NERP-2 (Neuroendocrine Regulatory Peptide-2)
A VGF peptide that boosts appetite and energy use through the brain's orexin system — one of a pair (NERP-1/-2) of neuroendocrine regulatory peptides. A research peptide, not a drug
NERP-2 — neuroendocrine regulatory peptide-2 — is a small amidated brain peptide cut from VGF, the same granin-like precursor that also yields TLQP-21. VGF is processed into a set of active peptides, and two of them are the 'NERPs': NERP-1 and NERP-2, released from neurons and endocrine cells by the regulated secretory pathway. NERP-2 is the more behaviourally active of the pair, and its signature is that it works through the orexin system — the brain's arousal-and-appetite circuit. Injected into the brain of rodents, NERP-2 increases food intake, raises energy expenditure, body temperature and movement, and speeds the stomach (more acid secretion and faster emptying); every one of these effects is blocked by orexin-receptor antagonists and is absent in orexin-deficient animals, placing NERP-2 squarely upstream of orexin. It also sharpens the pancreas's release of insulin when blood sugar is high. Its sister peptide NERP-1 does different things — it facilitates penile erection by acting in a separate brain region, and its level is altered in the blood of people with ALS, making it a candidate biomarker. Both peptides must be amidated at their tail to be active. NERP-2 and NERP-1 are studied as research peptides; they are not approved medicines and have not been given to people as a treatment.
No established human dose Details ↓
Recommended Dosing
No established human dose
NERP-2 and NERP-1 are endogenous VGF-derived peptides that have never been given to people as a treatment. The human study measures NERP-1 as an ALS marker, and the functional work is in animals and cells, where NERPs are given into the brain at experimental amounts that do not carry over to people.
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What is it?
VGF is a granin-like precursor protein stored in the regulated secretory granules of neurons and endocrine cells and cut into a family of active peptides (TLQP-21 is one, covered separately). Two of its products are the neuroendocrine regulatory peptides, NERP-1 and NERP-2 — amidated peptides from distinct regions of VGF (roughly residues 282-306 and 313-350 of the human precursor). They were identified as bioactive peptides of this regulated pathway, and NERP-2 is the more behaviourally active of the two; C-terminal amidation is required for the activity of both (the glycine-extended, non-amidated forms are inactive).
NERP-2's defining action is on feeding and energy, and it works through the orexin system. Given into the cerebral ventricles of rats, NERP-2 — but not NERP-1 or non-amidated NERP-2 — increases food intake, and it also raises body temperature, oxygen consumption and locomotor activity. NERP-2 is made in the lateral hypothalamus and perifornical region, where it co-localises with orexin neurons and switches them on, and neutralising the body's own NERP-2 with an antibody reduces food intake. Crucially, all of these effects are blocked by orexin-receptor antagonists and do not occur in orexin-deficient mice — so NERP-2 acts upstream of orexin to drive appetite and arousal.
The orexin link extends to the gut. Central NERP-2 increases gastric acid secretion and gastric emptying, effects blocked by an orexin-1-receptor antagonist and by atropine (which blocks the vagus nerve), and accompanied by neuronal activation in the lateral hypothalamus and the vagal motor nucleus. NERP-2 also has a pancreatic role: it potentiates glucose-stimulated insulin secretion from beta-cell lines and islets by raising intracellular calcium, where it co-localises with insulin — although a separate chronic-exposure study found that sustained NERP-2 can instead blunt insulin secretion and down-regulate beta-cell genes, and that NERP-2 rises in diabetic pancreas, so its pancreatic effect depends on context and duration.
NERP-1 does different things. Injected into the arcuate nucleus it facilitates penile erection — through a mechanism not related to orexin or oxytocin — while having little effect on feeding, the mirror image of NERP-2. And in people, NERP-1 is of interest as a disease marker: its immunoreactivity is raised in the plasma of patients with amyotrophic lateral sclerosis (ALS), a motor-neuron disease, suggesting it could serve as a blood biomarker, though in a motor-neuron cell model NERP-1 did not protect against oxidative stress.
NERP-2 and NERP-1 are endogenous VGF-derived research peptides. No published study has given them to people as a treatment — the human work measures NERP-1 as a marker, and the functional work is in animals and cells — they are approved nowhere, and material sold online as 'NERP-2' is an unregulated research chemical. Nothing here is a dose or a therapy; this page records what the published science says about the peptides.
Mechanism of Action
NERP-1 and NERP-2 are amidated peptides cut from the VGF precursor (with TLQP-21), active only when amidated. NERP-2 acts upstream of the orexin system to drive feeding, energy expenditure and gastric function, and potentiates glucose-stimulated insulin secretion; NERP-1 facilitates penile erection and is a candidate ALS biomarker. Their own receptor is not established (NERP-2 works via orexin neurons).
VGF processing
NERP-1 and NERP-2 are processed from the VGF precursor (with TLQP-21) and require C-terminal amidation for activity (PMIDs 20551287, 23111332).
Orexin-pathway feeding, energy and gastric control (NERP-2)
Central NERP-2 activates hypothalamic orexin neurons to increase food intake, energy expenditure and gastric acid/emptying — all orexin-receptor-dependent (PMIDs 20551287, 28213131).
Insulin, erection and ALS marker
NERP-2 potentiates glucose-stimulated insulin secretion acutely but blunts it chronically (PMIDs 23111332, 25529453); NERP-1 facilitates erection via the arcuate nucleus and is altered in ALS plasma (PMIDs 22561139, 39933412).
Published Research
These are studies of the neuroendocrine regulatory peptides read from their PubMed abstracts on November 6, 2026. They include animal studies of NERP-2's orexin-dependent control of feeding, energy and gastric function and of its potentiation of insulin secretion, a comparison of NERP-1 and NERP-2 on feeding and erection, a cell study of their chronic effect on beta-cells, and a human study of NERP-1 as an ALS plasma biomarker. The NERPs have not been given to people as a treatment; the human work is biomarker measurement.
NERP-2 regulates feeding via the orexin system
In rats, intracerebroventricular NERP-2 — but not NERP-1 or a non-amidated form — increased food intake, body temperature, oxygen consumption and locomotor activity. NERP-2 localised to the lateral hypothalamus, co-localised with and activated orexin neurons, and anti-NERP-2 antibody reduced food intake; the effects were abolished by orexin antibodies or orexin-receptor antagonists and did not occur in orexin-deficient mice — showing NERP-2 controls feeding and energy homeostasis upstream of orexin (a preclinical result).
NERP-2 potentiates glucose-stimulated insulin secretion
NERP-2 increased glucose-stimulated insulin secretion dose-dependently from the beta-cell line MIN6 and isolated mouse islets (not under low glucose), while NERP-1 and non-amidated NERP-2 did not, and it augmented insulin secretion when given intravenously or intraperitoneally to rodents. NERP-2 co-localised with insulin in islets and raised intracellular calcium — indicating it enhances insulin release by elevating beta-cell calcium (a preclinical result).
NERP-2 regulates gastric acid and emptying via orexin
Central (but not peripheral) NERP-2 increased gastric acid secretion and gastric emptying in rats, blocked by an orexin-1-receptor antagonist (SB334867), and induced Fos in the lateral hypothalamus and the dorsal motor nucleus of the vagus; atropine completely blocked the acid response — showing NERP-2 activates the orexin pathway and vagal output to drive gastric function (a preclinical result).
NERP-1 and NERP-2 differ: erection vs feeding
Injected into rat brain regions, NERP-2 (not NERP-1) increased feeding when given into the lateral ventricles or lateral hypothalamus, an orexin-1-receptor-dependent effect; conversely NERP-1 (not NERP-2) induced penile erection when given into the lateral ventricles or arcuate nucleus, by a mechanism unrelated to orexin or oxytocin. The two VGF peptides have distinct, site-specific actions (a preclinical result).
Chronic NERP effects on beta-cells
NERP-1 and NERP-2 are expressed in human pancreatic islets, including in diabetic pancreas. When INS1 cells and rat islets were incubated with NERPs for three days, glucose-stimulated insulin secretion was blunted, the readily-releasable insulin-granule pool shrank, and NERP-2 down-regulated insulin-granule proteins and beta-cell transcription factors (BETA2/NeuroD, Pdx-1, FOXO1) — suggesting chronic NERP-2 is an endogenous suppressor of glucose-dependent insulin secretion, with levels increased in diabetes (a cell study).
NERP-1 is altered in ALS plasma
Measuring VGF peptides by ELISA in the plasma of amyotrophic lateral sclerosis (ALS) patients (n=46 early and advanced vs 46 controls), only NERP-1 immunoreactivity was changed (elevated) across all ALS samples, while Parkinson's-disease controls were unchanged. In a motor-neuron-like cell line, NERP-1 fell inside stressed cells but rose in the medium and did not protect against oxidative stress — proposing NERP-1 as a possible ALS blood biomarker (a human observational study).
No Established Human Dose
NERP-2 and NERP-1 are endogenous VGF-derived peptides that have never been given to people as a treatment. The human study measures NERP-1 as an ALS marker, and the functional work is in animals and cells, where NERPs are given into the brain at experimental amounts that do not carry over to people. No regulator has approved any dose, and no published human dose exists, so no amount is printed here.
What this rests on: PMID 20551287, PMID 23111332, PMID 28213131.
Educational information, not medical advice. The doses on this page come from approved labels, published studies and, where no study exists, amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no label and no published test that says what forms or vial sizes NERP-2 (Neuroendocrine Regulatory Peptide-2) is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
Unknown: no human dose of NERP-2 (Neuroendocrine Regulatory Peptide-2) has been established (see No Established Human Dose below), so there is no amount to work out. The reconstitution calculator does the arithmetic for any vial, water and dose.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store NERP-2 (Neuroendocrine Regulatory Peptide-2), before or after mixing. The mixing guide sets out the general rules, with their sources: keep a mixed vial in the fridge, and use it promptly, as the bacteriostatic water label says of any drug dissolved in it. The 28 days often quoted is the limit for an opened multiple-dose vial from a manufacturer, an outer limit set for sterility, not a time a mixed solution has been shown to keep. Nobody has published how long NERP-2 (Neuroendocrine Regulatory Peptide-2) stays intact once mixed.
How it is taken
Unknown: with no established human dose, there is no established way of taking NERP-2 (Neuroendocrine Regulatory Peptide-2). What the human studies gave and how is set out under No Established Human Dose.
What to expect, and when
How long it stays in the body: a half-life of not established for humans as a drug; endogenous VGF-derived peptides. After about five half-lives almost none is left.
When effects appear: unknown; no source on this page gives a time to effect for NERP-2 (Neuroendocrine Regulatory Peptide-2). Results reported in the studies are under Published Research.
Source: half-life: PMID 20551287.
Side effects, and when to stop or get help
From the Side Effects section: No human adverse-event data exist: no published study has administered NERP-2 or NERP-1 to people; In animals, central NERP-2 increases appetite, energy expenditure and gastric activity via orexin (PMIDs 20551287, 28213131) and alters insulin secretion (PMIDs 23111332, 25529453) — preclinical signals, not a human safety profile; Chronic NERP-2 can suppress insulin secretion and is increased in diabetic pancreas (PMID 25529453); Material sold online as 'NERP-2' is an unregulated research chemical of unverified content. Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping NERP-2 (Neuroendocrine Regulatory Peptide-2). Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“The NERPs are research peptides that have not been given to people as a drug, so there is no human safety profile; the points below reflect that research status”).
Interactions
Unknown: a PubMed search for human interaction studies of NERP-2 (Neuroendocrine Regulatory Peptide-2) (reviewed 2026-11-06) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of NERP-2 (Neuroendocrine Regulatory Peptide-2) products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Research Chemical (Not a drug: Drugs@FDA and the openFDA label endpoint hold no record, and FDA GSRS and ChEMBL hold no substance record for NERP-2 or NERP-1 (searched November 6, 2026)). Sport: Not on the 2026 List.
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
The NERPs are research peptides that have not been given to people as a drug, so there is no human safety profile; the points below reflect that research status.
Contraindications & Cautions
The NERPs have no approved use and no label. These points reflect their research status.
Legal Status
NERP-2 and NERP-1 are endogenous VGF-derived peptides studied as research compounds; they are not drugs and are not approved in any country.
Frequently Asked Questions
?What is NERP-2?
NERP-2 (neuroendocrine regulatory peptide-2) is an amidated peptide cut from the VGF precursor — the same precursor as TLQP-21. It is one of a pair, NERP-1 and NERP-2.
?What does it do?
NERP-2 works through the brain's orexin system to increase food intake, energy expenditure and gastric acid/emptying (PMIDs 20551287, 28213131) and potentiates glucose-stimulated insulin secretion (PMID 23111332). NERP-1 instead facilitates penile erection (PMID 22561139) and is altered in ALS plasma (PMID 39933412).
?How is it related to TLQP-21?
All three are peptides cut from the VGF precursor. Grey Peptides has a separate entry for TLQP-21. C-terminal amidation is required for the NERPs to be active.
?Is it approved or available to buy?
No. NERP-2 (and NERP-1) are not medicines, have no FDA application or label, and are approved nowhere. Material sold online as NERP-2 is an unregulated research chemical. Grey Peptides lists no sellers and recommends no source; this page records the published science.
References
- [animal] Toshinai K, et al. "Neuroendocrine regulatory peptide-2 regulates feeding behavior via the orexin system in the hypothalamus." Am J Physiol Endocrinol Metab, 2010;299(3):E394-401. PMID: 20551287.
- [animal] Moin AS, et al. "Neuroendocrine regulatory peptide-2 stimulates glucose-induced insulin secretion in vivo and in vitro." Biochem Biophys Res Commun, 2012;428(4):512-7. PMID: 23111332.
- [animal] Namkoong C, et al. "NERP-2 regulates gastric acid secretion and gastric emptying via the orexin pathway." Biochem Biophys Res Commun, 2017;485(2):409-413. PMID: 28213131.
- [animal] Melis MR, et al. "Neuroendocrine regulatory peptide-1 and neuroendocrine regulatory peptide-2 influence differentially feeding and penile erection in male rats: sites of action in the brain." Regul Pept, 2012;177(1-3):46-52. PMID: 22561139.
- [mechanism] Kim JW, et al. "Chronic effects of neuroendocrine regulatory peptide (NERP-1 and -2) on insulin secretion and gene expression in pancreatic β-cells." Biochem Biophys Res Commun, 2015;457(2):148-53. PMID: 25529453.
- [clinical-trial] Noli B, et al. "NERP-1 modifications in amyotrophic lateral sclerosis." Tissue Cell, 2025;93:102780. PMID: 39933412.
- [other] UniProt O15240 (VGF neurosecretory protein, VGF gene), read November 6, 2026: the neuroendocrine regulatory peptides NERP-1 and NERP-2 are amidated peptides processed from the VGF pro-peptide (approximately VGF residues 282-306 and 313-350 of human proVGF); VGF is the same precursor that yields TLQP-21. https://www.uniprot.org/uniprotkb/O15240/entry
- [other] NERP-1 and NERP-2 were identified as VGF-derived amidated peptides of the regulated secretory pathway; NERP-2's orexin-dependent actions on feeding, energy expenditure and gastric function, its potentiation of insulin secretion, and NERP-1's pro-erectile and ALS-biomarker roles are from the studies carded on this page (read November 6, 2026). C-terminal amidation is required for activity.
- [other] US FDA, Drugs@FDA and the drug label endpoint (openFDA), searched November 6, 2026: no application and no label record for NERP-1 or NERP-2. They are endogenous VGF-derived peptides, not registered drugs; FDA GSRS and ChEMBL hold no substance record for them.
Sources & Citations
The six studies carded above were read from their PubMed records on November 6, 2026. Identity comes from UniProt (O15240, VGF): NERP-1 and NERP-2 are amidated peptides processed from VGF (with TLQP-21). NERP-2's orexin-dependent control of feeding, energy expenditure and gastric function, its potentiation (and chronic suppression) of insulin secretion, NERP-1's pro-erectile action, and NERP-1's alteration in ALS plasma are from the studies carded on this page; the absence of US approval and of a drug substance record from Drugs@FDA, openFDA, FDA GSRS and ChEMBL was checked the same day. Grey Peptides sells nothing and links to no vendor.
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