SHLP6
One of six small humanin-like peptides encoded in mitochondrial DNA: its sequence is unusually conserved, and 2025 zebrafish studies reported antioxidant and neuroprotective effects. Research-only.
A mitochondrial-derived peptide in the SHLP1–SHLP6 family. Notably distinct from humanin, SHLP2, and MOTS-c in its reported pro-apoptotic effect in multiple cell-culture models, suggesting that the broader mitochondrial-derived peptide family includes members with opposing regulatory roles rather than all acting as uniformly cytoprotective. Research-only; no clinical development.
Mechanism of action
Proposed pro-apoptotic activity — contrasting with humanin, SHLP2, and MOTS-c. The biological significance of this is debated; one hypothesis is that SHLP6 represents an "off-switch" balancing the prosurvival effects of other mitochondrial-derived peptides. Molecular target and receptor engagement are not established.
Primary uses
- Mitochondrial-derived peptide biology research (preclinical)
- Apoptosis-regulation research (cell culture)
Typical dosing
⚠ No human dosing established. Any human use would be unregulated and unsupported.
Regulatory status
Not FDA-approved. Research-only. No registered clinical trials.
Status as of this entry's last review, October 4, 2026. Approvals, compounding rules and sport rules change; the regulatory tracker is checked more often.
What we checked
SHLP6 was named in a 2016 paper that found six small peptides encoded in mitochondrial DNA. Its study cards below are sequence analyses and zebrafish work; this section records what can be checked about the discovery and its status.
Identity, computed
| Sequence | Not established |
SHLP6 is read from an alternative frame of the mitochondrial 16S ribosomal RNA gene, near humanin. Its sequence was reported by the discovering group; this entry does not print it because we have not read it in a source we can cite.
Regulatory status, read October 5, 2026
Drugs@FDA: 0 records for “SHLP6”. EMA medicines list: 0 records for “SHLP6”. Run for semaglutide, the same queries return 6 and 5 records (and the registry search 84 trials), so a zero here is an absence, not a broken search. Not named on the WADA 2026 and 2027 Prohibited Lists. As a substance with no current approval for human therapeutic use, it falls under section S0 (non-approved substances), which is prohibited at all times; the lists were read on September 27, 2026.
What the maker or sellers claim
Claim, from research-chemical sellers: SHLP6 is an anti-ageing or neuroprotective peptide for people. No study has given it to a person.
About the SHLP family, not SHLP6 alone
The 2016 discovery paper found six small humanin-like peptides by searching the same mitochondrial region as humanin. They differed in their effects on cell survival; the authors focused on SHLP2 and SHLP3, which reduced apoptosis and reactive oxygen species and improved insulin sensitivity in rats. SHLP6 was not one of the protective ones in that first screen (Cobb et al., 2016). Our SHLP family hub covers the others.
What we looked for and did not find
No human study, no registry record, no published sequence in a source we read and no regulator record.
| Source | Query | Results, October 5, 2026 | What it was |
|---|---|---|---|
| PubMed | SHLP6 | 11 | sequence, ground-squirrel and zebrafish studies |
| PubMed | small humanin-like peptides | 32 | the 2016 discovery paper and reviews |
| ClinicalTrials.gov | humanin-like | 0 | |
| Drugs@FDA (openFDA) | SHLP6 | 0 | |
| EMA medicines list | SHLP6 | 0 |
What the studies show
The studies that followed the 2016 discovery paper are sequence analyses and animal work; none has given SHLP6 to people. They are described here as their abstracts state them.
Analysis · 2023
A conserved sequence
Comparing the eight peptides encoded in the mitochondrial ribosomal genes (humanin, MOTS-c and SHLP1 to SHLP6), humanin and SHLP6 showed strong synonymous codon bias and sequence conservation, a sign of selection, while SHLP1, 2, 3 and 5 were poorly conserved.
Animal · 2023
Hibernation and heterothermy
A mitochondrial polymorphism in SHLP6, m.3017C>T, related to heterothermy, and in thirteen-lined ground squirrels the SHLP6 transcript in brown fat was higher before hibernation and during arousals than during torpor.
Animal · 2025
Modelling and zebrafish
Structural modelling predicted SHLP6's fold, and in stressed zebrafish larvae SHLP6 restored locomotor activity, raised IL-10 and reduced protein aggregation in a test with bovine serum albumin, which the authors read as antioxidant and anti-inflammatory.
Animal · 2025
Copper-induced neurotoxicity
In zebrafish exposed to copper sulfate, SHLP6 improved acetylcholinesterase levels and locomotion and raised antioxidant gene expression; its effects on inflammatory genes were mixed (TNF-α and NLRP3 up, IL-10 up).
References
- [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.
- [pubmed] Gruschus JM, et al. "Evidence of natural selection in the mitochondrial-derived peptides humanin and SHLP6." Sci Rep, 2023;13(1):14110. PMID: 37644144.
- [pubmed] Emser SV, et al. "Mitochondrial polymorphism m.3017C>T of SHLP6 relates to heterothermy." Front Physiol, 2023;14:1207620. PMID: 37675281.
- [pubmed] Kannan HT, et al. "In-silico modeling of SHLP6: A novel mitochondrial peptide controlling neurodegeneration and cellular aging." Comput Biol Med, 2025;197(Pt A):111054. PMID: 40915070.
- [pubmed] Thamarai Kannan H, et al. "SHLP6: a novel NLRP3 and Cav1 modulating agent in Cu-induced oxidative stress and neurodegeneration." Front Mol Neurosci, 2025;18:1553308. PMID: 40292418.
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Guides & tools
This entry is for educational purposes only and does not constitute medical advice. Dosing information reflects published regulatory or research data and is not a recommendation. Many compounds described here are not approved for human use in the United States. Consult a licensed medical professional before considering any peptide therapy.