SHLP2
SHLP2, small humanin-like peptide 2
Written by Aaron CuhaReviewed Sep 2026
Also known as: SHLP-2, small humanin-like peptide 2, MDP SHLP2
In plain English, from Aaron
This is how I would explain it to a friend. The evidence, with the numbers, is further down the page.
SHLP2 is a short peptide your own mitochondria make and release. Think of it as a text message from the power plants in your cells. Levels drop as you get older. It has a known receptor and a real story in mice. No human being has ever been given it.
What people take it for
- Better blood sugar and insulin response.
- Fat loss, because of the mouse results.
- Protecting the eyes as they age.
- General anti aging, since the peptide falls as you get older.
What the trials actually showed
There are no human trials. None. Not one person has been given this peptide in any study, and nothing is registered. In male mice, giving it protected them from getting fat on a high fat diet and improved their insulin. That result is solid and it is in mice. In cells it cut damage and helped the mitochondria work. The human side is only measuring, not giving. Levels fall with age. People who inherit a certain version of it get less Parkinson's disease. And here is the part the sales pages skip. In people without diabetes, higher levels of this peptide went along with more belly fat and more liver fat. That is the opposite direction from the mouse result. Across this whole family of peptides there is one registered human trial in the world, it is for a different one, and it will not report until 2028.
What people report
Reports, not trial results
The good
- There is almost nothing to report, because so few people have access to it.
- The handful of forum reports mention more energy, which is what people report for nearly every peptide.
The bad
- No side effect profile exists, because no human has been dosed in a study.
- Anything sold under this name is a research chemical with no purity testing.
- The one human measurement runs the wrong way, which should slow you down.
- The blood tests used in these studies are off the shelf kits that nobody has independently checked.
Where these come from: The mouse and cell results are published studies. The energy reports are scattered forum posts. There are no trial exit interviews or side effect tables, because there have been no trials.
My bottom line
This is good biology and zero human evidence, and those are not the same thing. I would watch this one for another five years rather than buy it.
An opinion, not a finding. I am a coach, not a doctor.
Overview
A mitochondrial-derived peptide with an identified receptor, a mouse obesity result and a human genetic association with protection against Parkinson's disease. It has never been administered to a person, and no trial is registered.
In 2016 a search of the same stretch of mitochondrial 16S ribosomal RNA that encodes humanin turned up six more short open reading frames. Those became SHLP1 through SHLP6, the small humanin-like peptides. SHLP2 is the one with a literature.
The mouse and cell work is better than most things in this category. SHLP2 and SHLP3 reduced apoptosis and reactive oxygen species and improved mitochondrial metabolism in vitro and enhanced preadipocyte differentiation in culture. Infused into the brain, SHLP2 increased glucose uptake and suppressed hepatic glucose production in rodent clamp studies. In 2023 a receptor was identified: SHLP2 binds and activates CXCR7, and systemic or intracerebroventricular SHLP2 protected male mice from high fat diet obesity and improved insulin sensitivity through POMC neurons in the arcuate nucleus.
The human side is entirely observational, and the word to hold onto is measured. Circulating SHLP2 declines with age. Plasma SHLP2 associates positively with android fat and liver fat in people without diabetes. Circulating mitochondrial-derived peptide levels differ by race in a prostate cancer context. And a naturally occurring SHLP2 variant is described as protective in Parkinson's disease, which is a genetic association in people rather than a drug effect.
Nobody has given SHLP2 to a human being. There is no registered trial. Across the entire mitochondrial-derived peptide class there is exactly one registered interventional human trial anywhere in the world, it is for MOTS-c, and it will not read out before 2028.
Mechanism of action
Encoded in the mitochondrial genome, in the 16S rRNA region, and released to act as a signalling peptide. The identified receptor is CXCR7, an atypical chemokine receptor. Downstream, SHLP2 acts on POMC neurons in the hypothalamic arcuate nucleus to influence energy homeostasis in mice, and in cells it reduces apoptosis and reactive oxygen species and supports mitochondrial metabolism. The general class hypothesis is that mitochondria signal their functional state to the rest of the body using these peptides, and that the signal weakens with age because the peptides decline.
Human evidence
Observational only. SHLP2 has been measured in human plasma and studied as an inherited variant, and has never been given to a person in any published or registered study.
- Circulating SHLP2 declines with age in human plasma, reported in the 2016 naming paper.
- In people without diabetes, plasma SHLP2 associated positively with android fat and liver fat.
- Circulating mitochondrial-derived peptide levels differ by race in a prostate cancer context, reported in 2022.
- A naturally occurring SHLP2 variant is described as protective in Parkinson's disease, a genetic association study.
- No administration study in humans. No registered clinical trial for SHLP2 on ClinicalTrials.gov.
What this does not tell you: Measuring a peptide and giving a peptide answer different questions. Every human finding here is compatible with SHLP2 being a marker of something else entirely, and the plasma association runs in the opposite direction to the mouse intervention result, which should slow anyone down. There is a second, quieter problem: most circulating measurements in this literature are made by commercial immunoassay, and the assay validation status of the mitochondrial-derived peptide literature has not been independently established. The irisin episode is the cautionary example of a field built on unvalidated ELISAs.
Reading the research record
SHLP2 is best read as one member of a class, because the class-level summary is the honest one. The mitochondrial-derived peptides now comprise humanin and its nuclear-encoded isoforms, MOTS-c, and SHLP1 through SHLP6. As of this review date there is exactly one registered interventional human trial of any mitochondrial-derived peptide anywhere in the world, it is for MOTS-c, it is recruiting, and it will not report before 2028.
Every other piece of human data in the entire class is observational: levels measured in plasma, muscle, semen or cerebrospinal fluid and correlated with age, exercise, fat mass or disease. Those observations are genuine and they are interesting. They are not evidence that administering the peptide does anything.
Among the six SHLPs, SHLP2 carries nearly all of the literature. SHLP1 and SHLP4 through SHLP6 are barely characterised beyond the naming paper, and anything sold or written about them is extrapolation from SHLP2 and humanin.
The evidence, charted
Fig. 1 · evidence composition
2of 6 citations (33%) are in people
Counted from the citation list on this page. The Human count is the same number shown in the badge at the top. Both understate any literature larger than the sources we cite.
Fig. 2 · evidence over time
Evidence spans 6 distinct years, 2016 to 2024, counted from the citation list on this page.
Fig. 3 · legal status at a glance
US
Not approved
UK
Not approved
AU
Not approved
CA
Not approved
Not approved in any of the four jurisdictions shown. A jurisdiction's classification is a regulatory fact, not a verdict on the science; see Legal status below for the full text and any notes.
Fig. 4 · dose response
No human dose response curve exists
We draw this figure where the data supports it. For this compound in humans it does not, so the panel stays empty rather than borrowing an animal curve and implying it transfers.
Key studies & citations
- In vitro2016
Naturally occurring mitochondrial-derived peptides are age-dependent regulators of apoptosis, insulin sensitivity, and inflammatory markers.
The naming paper. An in silico search of the 16S rRNA region of mitochondrial DNA that encodes humanin found six more short open reading frames, SHLP1 to SHLP6. SHLP2 and SHLP3 reduced apoptosis and reactive oxygen species and improved mitochondrial metabolism in vitro and enhanced 3T3-L1 preadipocyte differentiation in culture. Rodent clamp studies showed intracerebrally infused SHLP2 increasing glucose uptake and suppressing hepatic glucose production. It also reports that circulating SHLP2 declines with age in human plasma, which is a measurement, not an intervention.
Aging (Albany NY) - Animal2023
Mitochondria-derived peptide SHLP2 regulates energy homeostasis through the activation of hypothalamic neurons.
Identifies CXCR7 as the receptor SHLP2 binds and activates. Systemic and intracerebroventricular SHLP2 protected male mice from high fat diet induced obesity and improved insulin sensitivity, acting through POMC neurons in the arcuate nucleus. Male mice. This is the strongest mechanistic paper on the peptide and it is entirely preclinical.
Nature Communications - Human2021
Plasma mitochondrial derived peptides MOTS-c and SHLP2 positively associate with android and liver fat in people without diabetes.
Human plasma measurement in people without diabetes. Both MOTS-c and SHLP2 associated positively with android fat and liver fat. Worth reading carefully: the direction is positive, meaning higher peptide with more fat, which does not sit neatly with the mouse story in which giving the peptide protects against diet-induced obesity. An association in one direction and an intervention in the other are not in conflict, but neither can be used to predict the other.
Biochimica et Biophysica Acta, General Subjects - Human2024
A naturally occurring variant of SHLP2 is a protective factor in Parkinson's disease.
Human genetics. A naturally occurring SHLP2 variant is described as protective against Parkinson's disease. This is the strongest human signal attached to the peptide and it concerns inheriting a variant, not taking a peptide. Nobody in this study was given SHLP2.
Molecular Psychiatry - In vitro2018
Characterizing the protective effects of SHLP2, a mitochondrial-derived peptide, in macular degeneration.
Retinal pigment epithelium cell work relevant to age-related macular degeneration, reporting protective effects against oxidant injury. Cell culture. The eye claim that circulates for this peptide traces to work at this level, not to any patient.
Scientific Reports - Animal2019
Metabolomic profile of diet-induced obesity mice in response to humanin and small humanin-like peptide 2 treatment.
Diet-induced obese mice treated with humanin and with SHLP2, profiled by metabolomics. Mice. Included because it is one of the few papers that actually administers the peptide to a living animal rather than measuring it.
Metabolomics
Frequently asked questions
Has anyone taken SHLP2?
Not in any published or registered study. There is no human administration data and no registered trial. Across the whole mitochondrial-derived peptide class there is one registered interventional trial, for MOTS-c, not reading out before 2028.
Does SHLP2 cause weight loss?
In male mice, systemic or brain-infused SHLP2 protected against high fat diet obesity and improved insulin sensitivity through POMC neurons. In humans, plasma SHLP2 associates positively with android and liver fat, which is the opposite direction. Neither of those is a weight loss result in a person.
What is the difference between SHLP2 and humanin?
They are encoded in the same region of mitochondrial DNA and were found the same way. Humanin came first and has the larger literature and the observational trials. SHLP2 was one of six additional reading frames identified in 2016 and has its own receptor, CXCR7. Neither has been administered to a person.
What about SHLP1, SHLP3, SHLP4, SHLP5 and SHLP6?
SHLP3 appears alongside SHLP2 in the original in vitro work on apoptosis and reactive oxygen species. The rest are essentially uncharacterised past the paper that named them. If a product page describes what SHLP5 does, it is extrapolating.
Is the Parkinson's finding a reason to take it?
No. That study reports that people who inherit a particular SHLP2 variant have lower Parkinson's risk. Inheriting a variant for a lifetime and injecting a peptide are different exposures, and no one has tested the second.