SHLP2
Small Humanin-Like Peptide 2
Evidence grade 1 of 5, Untested. Read how the Atlas grades evidence.
SHLP2 is a mitochondrial-derived peptide encoded within the MT-RNR2 (16S rRNA) region of mitochondrial DNA, the same locus that encodes Humanin, discovered in silico by the Pinchas Cohen laboratory at USC and reported in 2016. Its bioactivity rests on cell-culture and rodent work, including anti-apoptotic and metabolic effects in retinal pigment epithelium (Nashine 2018) and protection from diet-induced obesity with improved insulin sensitivity via hypothalamic POMC neurons in mice (Kim 2023). Human data are observational only, associating lower circulating SHLP2 with prostate cancer risk in a 200-man case-control study (Xiao 2017) and a naturally occurring K4R variant with reduced Parkinson's risk (Miller 2023); there are no interventional human trials, so administered SHLP2 grades grade 1.
- FDA
- Not FDA approved for any indication; no approved drug application, no completed human clinical trials. Available only as a research reagent, not for human use.
- WADA
- Not specifically named on the WADA Prohibited List; peptides acting on metabolic and growth pathways may fall under broader WADA categories, so competing athletes should verify current status.
Reference only. Not medical advice.
What can go wrong
Very early stage with no human interventional data; safety, dosing, and long-term effects in humans are undefined.
Talk to a clinician before taking this. The Atlas can tell you what has been studied about SHLP2. It cannot tell you how it would interact with your body, your history, or anything else you are taking, and nothing on this page is a reason to start.
A member of the humanin family from the USC mitochondrial-peptide program. Higher plasma levels associate with longer survival; anti-apoptotic and neuroprotective in preclinical models.
What people take it for
These are the reasons people give for taking it. They are not effects it has been shown to have.
How it is supposed to work
SHLP2 (Small Humanin-Like Peptide 2) is one of a family of small peptides encoded in mitochondrial DNA, in the same region as humanin. In laboratory studies it is protective: it reduces cell death and oxidative stress, supports mitochondrial energy production, and improves insulin sensitivity. In mice, giving SHLP2 protected against diet-induced obesity and acted on appetite-controlling neurons in the brain. Unlike MOTS-c, it does not rise with exercise.
SHLP2 is a small mitochondrial-derived peptide, one of six small humanin-like peptides found by searching the same mitochondrial ribosomal gene that encodes Humanin. Like its family it is secreted and acts as a signal outside the mitochondria, and its circulating levels fall with age.
- Type
- Mitochondrial peptide
- Family
- Small humanin-like
- Action
- Protective, insulin-sensitizing
- Human trials
- None
- Approved
- No
- Key concern
- Cancer
The Protective, Insulin-Sensitizing Member Of The Humanin Family
SHLP2 is essentially Humanin’s metabolic-leaning relative, and it shares both Humanin’s appeal and Humanin’s cautions. The biology is real and interesting: it reduces apoptosis and oxidative stress, improves mitochondrial energy production, protects against amyloid toxicity in cells, and acts as a genuine insulin sensitizer in animal studies, both peripherally and through the brain, with levels declining as we age. But like the whole mitochondrial-peptide family, the evidence is preclinical and observational, with no completed human trials, no approval and no established dosing, so any longevity or metabolic use runs well ahead of the proof. And because its protective action includes blocking apoptosis, and it has promoted cell proliferation in some studies, it carries the same double edge as Humanin: a signal that keeps stressed cells alive could also shield malignant ones.
Safety in detail
Human evidence for SHLP2 is limited to observational blood-level associations. No dosing, safety, or efficacy has been established in people, and material sold for research use is not manufactured or tested to pharmaceutical standards.
- Effects are documented in cell culture and animal models; there are no completed human safety or efficacy trials.
- Not approved for any use; any consumer material is gray-market research-use-only with unverified identity, dose and purity.
- As an unstudied injectable, its long-term human safety is entirely unknown.
- Best understood as a research molecule, not a therapy.
Children and teenagers
SHLP2 has no validated pediatric use and is an unapproved peptide with a cancer concern. There is no appropriate pediatric use.
What people get wrong
Nothing recorded here yet. There is almost certainly something people get wrong about this one, and the blank space means we have not written it down, not that the record is clean.
Who profits, and who pushes back
Nobody is named here yet, because we have not done that work on this entry. Read that as unfinished. Somebody almost certainly sells this, and somebody almost certainly disputes it. Assume both until we have checked.
SHLP2 reaches users through the longevity gray market and research-reagent suppliers, the same channels and commercial interest that surround the mitochondrial-peptide family. There is no approved product, and its market runs on protective preclinical biology with no human proof.
How we got here
SHLP2 was identified in 2016 when the Pinchas Cohen laboratory at the University of Southern California ran an in silico search for small open reading frames inside the mitochondrial 16S ribosomal RNA gene (MT-RNR2), the same region that had earlier yielded Humanin. That search returned six short peptides named SHLP1 through SHLP6 for their homology to Humanin, with SHLP2 emerging as the most metabolically active. It has never been renamed or commercialized as an approved product and circulates in the literature and among research-peptide vendors under the same SHLP2 designation, with a distinct K4R sequence variant later described in the Parkinson's work.
SHLP2 was identified in 2016 when researchers searched the mitochondrial ribosomal region that encodes Humanin and found six additional small peptides, naming them small humanin-like peptides. SHLP2 emerged as one of the protective, metabolically active members.
The numbers behind the grade
- Type
- Mitochondrial peptide
- Family
- Small humanin-like (SHLP)
- Effects
- Cytoprotective, insulin
- Stage
- Preclinical
- Approved
- No
- Exercise-induced
- No
The people taking it
The most studied of the small humanin-like peptides and a notable name in the emerging mitochondrial-derived-peptide field, though still firmly a research molecule.
SHLP2’s users are longevity and metabolic-health biohackers drawn to the mitochondrial-peptide story, plus the research community studying these peptides.
Studied in research for cytoprotection, insulin sensitivity and metabolic regulation; it has no approved or established human use and appears in the consumer market only as a research peptide.
Set against the alternatives
SHLP2 is the metabolic-leaning, protective member of the mitochondrial-derived-peptide family, sitting close to Humanin and its potent analog. Against the sibling MOTS-c it overlaps on metabolism and insulin sensitivity, and against SHLP6 it is the opposite, protecting cells rather than killing them. Its profile is Humanin’s with a metabolic accent and the same cancer double-edge.
What we do not know
- Whether SHLP2’s protective and metabolic effects translate from mice to humans.
- What its receptor and precise mechanism are, still not fully defined.
- Whether it has therapeutic potential in metabolic or neurodegenerative disease.
Legal status
Not approved anywhere and not available as a therapeutic. It exists as a research compound and, where sold to consumers, as research-use-only material that is not for human use. The evidence is preclinical.
Status current as of July 2026. Regulatory positions change, sometimes quickly.
The market for this
What follows describes how this is bought and sold. It is not a buying guide and it is not an endorsement of any seller.
There is no approved route. It is available only as research-use-only material from peptide vendors, which is not intended for human use; given the absence of human data, self-experimentation is not advisable.
Not produced as a drug; any consumer-facing material is research-use-only, typically synthesized overseas in China, with no quality assurance and frequently no certificate of analysis.
What this entry does not yet cover
What follows is unfinished work on our side, not a finding about SHLP2.
- Timeline. We have not built the dated record of research and regulatory events.
- Supply chain. We have not mapped where it is made.
- What could change. No forward-looking summary yet.
Sources
SHLP1-SHLP6 including SHLP2 were discovered in silico from small ORFs in the mitochondrial 16S rRNA (MT-RNR2) gene by the Cohen lab at USC; peptides are 20-38 amino acids and share homology with Humanin.
Overview of the small humanin-like peptide family, MT-RNR2 origin, discovery year, and amino-acid lengths.
SHLP2 is anti-apoptotic and chaperone-like in aging retinal pigment epithelium and protects in a preclinical macular degeneration model (in-vitro and cell work).
SHLP2 binds CXCR7 and, given systemically or ICV, protected male mice from high-fat-diet obesity and improved insulin sensitivity via hypothalamic POMC neurons; a rodent/mechanistic study, not human.
A naturally occurring m.2158T>C variant yields a K4R form of SHLP2 with increased stability and is associated with reduced Parkinson's disease risk; a human genetic-association finding, not an intervention.
In 200 men undergoing biopsy, lower circulating SHLP2 was associated with higher prostate-cancer risk in white men; observational human marker study with a 350 pg/ml threshold, not a treatment trial.
PubMed record confirming the SHLP2 prostate-cancer marker study authorship and year.
SHLP2 is supplied by research-reagent vendors as a peptide for laboratory research use, not as an approved drug or supplement.
MedChemExpress, SHLP2 (Small humanin-like peptide 2) product listing
Evidence of natural selection acting on mitochondrial-derived peptides including the SHLP family, supporting their status as conserved MT-RNR2-encoded peptides.
Evidence of natural selection in the mitochondrial-derived peptides humanin and SHLP6, PMC
The studies that matter
Cohen group, MDP characterization2016
Identified the SHLP family and showed SHLP2 (with SHLP3) shares humanin’s cytoprotective effects, reducing apoptosis and reactive oxygen species and improving mitochondrial metabolism in vitro.
Energy-homeostasis study (Nature Communications)2023
In mice, systemic and brain administration of SHLP2 protected against high-fat-diet obesity and improved insulin sensitivity by activating hypothalamic appetite neurons.
Macular degeneration and chaperone studies2017-2018
SHLP2 protected retinal cell models and, like the potent humanin analog, showed chaperone-like activity against protein misfolding.