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Evidence: MediumPeptideResearch ChemicalMitochondrial-derived peptideMeasured in peopleNot a medicine

SHLP2

A small peptide encoded in mitochondrial DNA, protective in cells and mice and measured, not tested, in people

SHLP2 is one of six small humanin-like peptides encoded in the mitochondrial genome, described in 2016. In cells it reduced cell death and oxidative stress, and in rats it acted as an insulin sensitiser. In people it has only been measured: levels rose with abdominal fat in one study and differed by race in a prostate cancer study.

At a Glance Read Research →
Overview

What is it?

Most proteins are encoded in the cell nucleus, but the small DNA inside mitochondria also turns out to encode a few short peptides. Humanin was the first. In 2016 a search of the same stretch of mitochondrial DNA found six more, named small humanin-like peptides, and SHLP2 and SHLP3 shared humanin's protective effects.

In cells, SHLP2 reduced programmed cell death and reactive oxygen species and improved mitochondrial metabolism, and it encouraged pre-fat cells to mature. Infused into the brains of rats during insulin clamp studies, it increased glucose uptake and suppressed the liver's glucose output, which the authors read as insulin-sensitising.

Human research so far measures it in blood. In 125 Chinese adults without diabetes, SHLP2, like the related MOTS-c, was higher in people with metabolic syndrome and tracked abdominal fat and waist size. In a prostate cancer study, SHLP2 was lower in African American than European American men, and higher levels were linked to lower cancer risk only in European American men. Both are observational studies: they show associations at one point in time, not cause and effect, and neither tested giving SHLP2 to anyone.

SHLP2 has never been given to people, and these associations do not show that adding it would help. Research-grade products are untested for human use. Our SHLP family page and humanin entry cover the wider group.

Structured data

At a Glance

Every value in this table is printed from the Grey Peptides dataset, the same record the compound explorer and comparison tool read, so the three can never disagree.

ClassA 26-amino-acid mitochondrial-derived peptide encoded by an alternate reading frame within the 16S ribosomal RNA gene of mitochondrial DNA; the most-studied of the six small humanin-like peptides (SHLP1–SHLP6).
Sequence26 amino acids (Pro-Gly-Val-Lys-Phe-Leu-Lys-Ala-Thr-Gly-Gln-Pro-Pro-Pro-Pro-Leu-Pro-Trp-Ala-Phe-Lys-Ala-His-Pro-Ser-Leu — as reported by Cohen group)
Molecular weight2853.37 g/mol
Half-lifeNot formally characterized in humans
Typical doseNot established for human use
US statusResearch Chemical
Evidence levelMedium
Last reviewed2026-10-05
Evidence

Published Research

These studies were read from their PubMed abstracts on October 5, 2026.

In Vitro2016

Discovery of the SHLPs

Six small humanin-like peptides were identified in mitochondrial DNA; SHLP2 and SHLP3 reduced apoptosis and reactive oxygen species and improved mitochondrial metabolism in cells, and intracerebral SHLP2 increased glucose uptake and suppressed hepatic glucose production in rat clamp studies.

PMID: 27070352
Human2021

Blood levels and abdominal fat

In 125 Chinese adults without diabetes, plasma SHLP2 (mean 1,393 pg/mL in those with metabolic syndrome) was elevated with metabolic syndrome and associated most strongly with waist circumference and android fat.

PMID: 34419510
Human2022

Race and prostate cancer risk

SHLP2 and MOTS-c were lower in African American than European American control men; higher levels were associated with lower prostate cancer risk in European American men but not African American men.

PMID: 35789022
Animal2020

Humanin, the family's founder

Humanin overexpression extended lifespan in worms, and treating middle-aged mice with the humanin analogue HNG improved metabolic healthspan measures, context for why its relatives are studied.

PMID: 32575074
Safety

Side Effects & Contraindications

Reported Side Effects

Not applicable.

● SHLP2 has never been given to people as a treatment
● Any product sold as SHLP2 is untested for human use

Contraindications & Cautions

Not a medicine, so there is no label and no formal contraindication.

● No approved product exists; nothing sold as this peptide has been tested in people as a treatment
● Research-grade material has no quality control for human use
Questions

Frequently Asked Questions

?What is SHLP2?

A 26-amino-acid peptide encoded in mitochondrial DNA, one of six small humanin-like peptides described in 2016.

?Does SHLP2 help insulin sensitivity?

In rats, brain-infused SHLP2 acted as an insulin sensitiser; it has never been tested in people.

?Is SHLP2 the same as MOTS-c?

No, but both are mitochondrial-derived peptides, and in one human study both rose with abdominal fat.

Bibliography

References

  1. [pubmed] Cobb LJ, et al. "Naturally occurring mitochondrial-derived peptides are age-dependent regulators of apoptosis, insulin sensitivity, and inflammatory markers." Aging (Albany NY), 2016;8(4):796-809. PMID: 27070352.
  2. [pubmed] Sequeira IR, et al. "Plasma mitochondrial derived peptides MOTS-c and SHLP2 positively associate with android and liver fat in people without diabetes." Biochim Biophys Acta Gen Subj, 2021;1865(11):129991. PMID: 34419510.
  3. [pubmed] Ramirez-Torres A, et al. "Racial differences in circulating mitochondria-derived peptides may contribute to prostate cancer health disparities." Prostate, 2022;82(13):1248-1257. PMID: 35789022.
  4. [pubmed] Yen K, et al. "The mitochondrial derived peptide humanin is a regulator of lifespan and healthspan." Aging (Albany NY), 2020;12(12):11185-11199. PMID: 32575074.
  5. [pubmed] Mehta HH, et al. "Mitochondrial-derived peptides as biomarkers of aging and age-related diseases." Aging Cell, 2022;21:e13641.

Sources & Citations

Studies from their PubMed abstracts, read October 5, 2026.

Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Consult a licensed healthcare provider before making health decisions.

Last reviewed: 2026-10-05