SHLP-2
Research OnlyA 26-amino acid mitochondria-derived peptide (MDP) discovered in 2016 from the same mitochondrial DNA region as humanin. Shows cytoprotective, metabolic, and potential longevity effects in preclinical studies. Part of an emerging class of mitochondrial signaling molecules, but human therapeutic data is lacking.
Small Humanin-Like Peptide 2 · SHLP2 · Mitochondrial-Derived Peptide 2
3 human studies
- Preclinical
- 85%
- Clinical
- 15%
Based on 20 cited sources
Demonstrated effect magnitude — not a recommendation or safety claim.
Research Depth 38: best human evidence is an observational mtSNP genetic association linking the SHLP2 K4R variant to reduced Parkinson's risk (38167865, drawing on Framingham/HRS cohorts) — controlled observational (1A~18) but no study has ever administered SHLP-2 to humans, so risk-of-bias (1B~5), precision (1C~5) and directness (1D~3) are low; a substantial multi-model preclinical program (obesity/insulin-sensitizer mouse 37468558, PD toxin mouse 38167865, AMD RPE in vitro 30310092, IAPP chaperone 28798389, osteoblast 41315599, asthma 40935298) earns 1E~7. Mechanism 68: CXCR7 target identified by structural-complementation screen with binding + functional activation of POMC neurons via MAPK-ERK1/2 (37468558) plus complex-1 binding by mass spec (2A~30); proximal pathway mostly mapped (2B~20); limited dose-response (2C~9); confirmed in in-vivo mammalian models (2D~9). Plausibility 73: mechanism->surrogate markers (insulin sensitivity, mtDNA copy, OXPHOS, ROS) established with clinical benefit inferred (3A~25); coherent with mitochondrial aging biology (3B~22); strong same-class analogy from humanin/MOTS-c (3C~18); moderately broad multi-system claims trim specificity (3D~8). Global Coverage 46: originally one USC group but now independently replicated in South Korea (Yonsei 41315599) and China (Jiangnan 40935298) plus a 2026 Indiana review (4A~20, 4B~13), ~23 PubMed records (4C~13), no regulatory recognition (4D 0). Community Experience 30: niche enthusiast discussion only, short real-world track record, sparse and inconsistent reports, no adverse signal over minimal exposure. Effectiveness not established: no quantified human efficacy estimate (the only human data is a genetic-variant association, not an intervention) and no meaningful community effect signal.
The proposed mechanisms of SHLP-2 are based primarily on animal and in vitro studies. Human therapeutic data is lacking, though observational studies have identified protective genetic variants.
How It Works (Simplified)
SHLP-2 appears to act as a mitochondrial signaling molecule through several pathways:
Binds to chemokine receptor CXCR7, activating MAPK-ERK1/2 signaling cascade that regulates hypothalamic POMC neurons controlling appetite and thermogenesis.
Directly binds to mitochondrial complex 1, stabilizing this critical enzyme and protecting against dysfunction linked to neurodegeneration.
Exhibits chaperone-like properties, binding to misfolded protein seeds and preventing amyloid aggregation associated with metabolic and neurodegenerative diseases.
Activates anti-apoptotic pathways by reducing BAX/p53 and increasing BCL-2, while enhancing mitochondrial biogenesis through PGC-1a upregulation.
Key Research: Kim SK et al. (Nature Communications, 2023) identified CXCR7 as the receptor for SHLP-2 and demonstrated its role in hypothalamic energy regulation. PMID:37468558
Important Limitations
- Research is recent (discovery in 2016) with limited independent replication
- Most studies from a single research group (USC Cohen lab)
- No human therapeutic administration studies exist
- Translation from animal models to human physiology is unconfirmed
- Pharmacokinetics and bioavailability in humans not characterized
Based on preclinical observations: Initial receptor binding and signaling cascade activation may begin. Animal studies show metabolic parameter changes within days of administration. No human timeline data available.
PMID:37468558Animal studies suggest ongoing metabolic and mitochondrial effects. Mouse models showed improved insulin sensitivity and reduced weight gain during this period. Cytoprotective signaling likely established.
PMID:27070352Preclinical models show sustained metabolic improvements. Studies demonstrate continued mitochondrial biogenesis enhancement and maintained cytoprotective effects over several weeks of treatment.
PMID:30310092Long-term animal studies suggest persistent effects on mitochondrial function and metabolism. However, human pharmacokinetics, duration of effect, and optimal treatment length are completely unknown.
Research-based observations
This timeline reflects observations from published clinical and preclinical studies. Individual responses may vary significantly. This is not a guarantee of effects or a dosing schedule. Consult qualified healthcare providers for personalized guidance.
Good Signs (6 indicators)
Warning Signs (5 indicators)
Bad Signs (6 indicators)
For Research Evaluation Only
These quality indicators are general guidelines based on typical peptide characteristics. Professional laboratory testing (HPLC, mass spectrometry) provides definitive quality verification. This checklist is for initial visual evaluation only.
Humanin
SynergisticBoth are mitochondria-derived peptides from overlapping mtDNA regions. SHLP-2 and humanin share cytoprotective mechanisms but act through distinct receptors. Complementary protective effects likely without antagonism.
Mots-C
CompatibleDifferent mitochondria-derived peptide with metabolic effects. MOTS-C primarily affects AMPK pathway while SHLP-2 acts via CXCR7. Non-overlapping mechanisms suggest compatibility.
Shlp-6
CompatibleSame peptide family but different effects. SHLP-6 shows pro-apoptotic properties while SHLP-2 is anti-apoptotic. May have balancing effects in cellular stress response.
Ss-31
CompatibleBoth target mitochondria but through different mechanisms. SS-31 stabilizes cardiolipin while SHLP-2 binds complex 1. Potentially complementary mitochondrial support.
BPC-157
CompatibleNon-overlapping mechanisms. BPC-157 focuses on tissue repair while SHLP-2 provides mitochondrial protection. No known interactions or contraindications.
Research Note: Interaction data is based on published literature, mechanistic understanding, and theoretical considerations. Most peptide combinations lack direct clinical study. This information is for educational purposes only and does not constitute medical advice. Always consult qualified healthcare providers.
Key Studies Cited
Full reference list available on request. All citations link to PubMed for verification.
This dossier synthesizes available evidence from peer-reviewed literature, regulatory documents, and clinical trial registries. Evidence strength ratings follow a modified GRADE approach.
For complete methodology details, see our Methodology page.
Important Disclaimer
This dossier is for educational purposes only and does not constitute medical advice. Always consult a qualified healthcare provider before making health decisions.
Get Research Alerts
New dossiers and major study summaries delivered to your inbox. Evidence-graded, citation-backed research you can trust.
No spam. Unsubscribe anytime.
Compare SHLP-2
Related Peptides
Endoluten
Pineal cytamin · Pineal gland peptides · A-8 pineal peptides
A cytamin-class peptide supplement derived from pineal gland tissue, part of the Russian bioregulator framework. Marketed as an oral supplement for pineal function and melatonin support. Contains peptide complexes rather than defined sequences. No Western clinical validation.
Epithalon
Epitalon · Epithalone · AGAG +1
A synthetic tetrapeptide (Ala-Glu-Asp-Gly) developed by Russian scientist Vladimir Khavinson, claimed to activate telomerase and extend lifespan. 2025 independent Western research confirmed telomerase activation in vitro. Still not approved anywhere; no controlled human clinical trials.
FOXO4-DRI
FOXO4-D-Retro-Inverso · FOXO4-DRI Peptide · Proxofim
A D-retro-inverso peptide designed to disrupt the FOXO4-p53 interaction, selectively eliminating senescent cells (senolytic). Preclinical studies in aged mice demonstrated restored fitness, fur density, and renal function. No human clinical trials conducted. More selective than BCL-2 inhibitors but remains unproven in humans.
Glutathione
GSH · L-Glutathione · Reduced Glutathione +1
The master antioxidant and most abundant intracellular thiol in mammalian cells. This naturally occurring tripeptide (glutamate-cysteine-glycine) is essential for detoxification, immune function, and cellular protection. Extensively studied with strong mechanistic understanding and growing clinical evidence.
Klotho
Alpha-Klotho · KL protein · Anti-aging protein
An anti-aging transmembrane protein linked to longevity in animal models. Mouse studies demonstrate 15-20% lifespan extension. Primate cognition data published in Nature Aging. Klotho Neurosciences developing therapeutic applications for neurodegenerative disease.