SHLP2 Protocol

Dosing & Research

Last Updated: September 4, 2026

Also known as: Small Humanin-Like Peptide 2

Chemical Identity

Amino Acid Sequence: MGVKFFTLSTRFFPSVQRAVPLWTNS

Mitochondrial-derived peptide signaling research, Cytoprotection and stress-resistance models, Insulin-sensitivity and energy-homeostasis studies, Hypothalamic POMC neuron activation (animal)

Evidence Level

Preclinical Only

Species Studied

Mouse • In vitro

Half-Life

Not Well Characterized In Vivo

Administration

Not established (preclinical: systemic or intracerebroventricular in animal studies)

Frequency

Per study protocol; no established human schedule

How It Works

26-amino-acid peptide encoded within the mitochondrial 16S rRNA (MT-RNR2) region, structurally related to humanin. Preclinical studies report cytoprotective and insulin-sensitizing effects
systemic or intracerebroventricular administration activated hypothalamic POMC neurons, suppressed food intake, and protected against high-fat-diet-induced obesity in mouse models via binding to the chemokine receptor CXCR7.
Mitochondrial-derived peptide signaling research
Cytoprotection and stress-resistance models
Insulin-sensitivity and energy-homeostasis studies

Dosing Structure

Dose

Preclinical research only

Frequency

Per study protocol; no established human schedule

Notes

Circulating SHLP2 levels are reported to decline with age in the research literature, paralleling humanin. Studied alongside Humanin and MOTS-c as part of the broader mitochondrial-derived peptide family. Entirely preclinical (animal and in vitro); no human dosing or safety data established. Research and laboratory reference only.

Example Protocols

Dose: Preclinical research only

Frequency: Per study protocol; no established human schedule

Duration: Not Established In Humans

Off Period: Not listed

Calculate dosing →

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Protocol Notes

•

Circulating SHLP2 levels are reported to decline with age in the research literature, paralleling humanin.

•

Studied alongside Humanin and MOTS-c as part of the broader mitochondrial-derived peptide family.

•

Entirely preclinical (animal and in vitro); no human dosing or safety data established.

•

Research and laboratory reference only.

What Is SHLP2?

SHLP2 (Small Humanin-Like Peptide 2) is a 26-amino-acid peptide encoded within the mitochondrial 16S rRNA gene, part of a family of mitochondrial-derived peptides that also includes Humanin and MOTS-c. Preclinical research describes cytoprotective and insulin-sensitizing effects, and more recent work shows it activates hypothalamic neurons involved in appetite and energy expenditure in mouse models. It is an entirely preclinical research compound with no human dosing or safety data.

Research Observations - Not Medical Claims

▸Family characterization (Aging, 2016; PMID: 27070352): SHLP2 was identified alongside five related small humanin-like peptides (SHLP1-6) encoded in the mitochondrial 16S rRNA region; circulating SHLP2 levels were found to decline with age, and the peptide showed cytoprotective, insulin-sensitizing, and anti-apoptotic effects in cell and animal models.
▸Energy homeostasis (Nature Communications, 2023; PMID: 37468558): Systemic and intracerebroventricular administration of SHLP2 protected male mice from high-fat-diet-induced obesity and improved insulin sensitivity; SHLP2 activated POMC neurons in the hypothalamic arcuate nucleus, suppressing food intake and promoting thermogenesis, via binding to the chemokine receptor CXCR7.
▸Mechanistic novelty: The CXCR7 interaction identified via structural complementation screening represents a distinct receptor pathway from those used by other mitochondrial-derived peptides studied to date.

Evidence Summary

Preclinical OnlyNaturally occurring mitochondrial-derived peptide; not FDA-approved for any indication. For research and laboratory reference only -- no medical claims.

Evidence StrengthPreliminary