--- title: "Klotho" canonical_url: https://bestpeptidecalculator.app/library/klotho description: "Transmembrane and soluble anti-aging protein that is an FGF23 co-receptor. Shop “Klotho” vials are not an FDA-approved drug and are often fragments or poorly characterized proteins." updated: 2026-11-07 publisher: Peptide Library notice: "Research and educational use only. Not medical advice." --- # Klotho Klotho (also called α-Klotho or a-Klotho) is a longevity protein in the Longevity / FGF23 co-receptor class. Alpha-Klotho is a single-pass transmembrane protein expressed mainly in kidney and choroid plexus. Membrane-bound Klotho functions as an obligate co-receptor: FGF23 binds FGF receptors with low affinity alone, and Klotho is required to form a high-affinity complex, which is how FGF23 regulates phosphate excretion and vitamin D metabolism. Transmembrane and soluble anti-aging protein that is an FGF23 co-receptor. Shop “Klotho” vials are not an FDA-approved drug and are often fragments or poorly characterized proteins. Also known as: α-Klotho, a-Klotho, KL protein. Categories: Cognitive, Longevity, Experimental. ## Classification - Type: Longevity protein / research - Mechanism class: Longevity / FGF23 co-receptor - Development stage: Research only - Regulatory class: Research compound, not FDA-approved ## Mechanism Alpha-Klotho is a single-pass transmembrane protein expressed mainly in kidney and choroid plexus. Membrane-bound Klotho functions as an obligate co-receptor: FGF23 binds FGF receptors with low affinity alone, and Klotho is required to form a high-affinity complex, which is how FGF23 regulates phosphate excretion and vitamin D metabolism. The extracellular domain is also shed to produce soluble Klotho, which circulates and acts independently of FGF23, with reported effects on Wnt and insulin/IGF-1 signalling and on ion channel regulation. Klotho-deficient mice show a shortened lifespan with multiple ageing-like features, and overexpression extends it, which is the basis for interest in soluble Klotho in cognitive and vascular ageing. Human interventional data does not exist. Targets: FGFR/FGF23, Aging-related pathways. Origin: Endogenous protein; research reagents vary widely. ## Properties - Molecular weight: ~130 kDa (full-length protein) ## Evidence - Evidence level: Insufficient Evidence - Highest documented: Lab & animal studies - Human trials: 0 - Controlled human trials: 0 - Preclinical sources: 2 - Latest source: 2023 No human dose is established for this compound. Each step shows whether the sources Peptide Library has reviewed include that kind of research. Counts are reviewed sources, not every study ever published. Reviews and programme summaries that describe human use are shown as "reported", not as trials, and registered trials without published results are listed but not counted. A higher step means research has progressed further; it does not mean a compound works better or is safer. Compounds whose evidence has not been reviewed yet show "Not reviewed" instead of a guess. ### Studies 1. Longevity factor klotho enhances cognition in aged nonhuman primates. Nat Aging. 2023. 2023. Preclinical: animal or lab study. Population: Aged rhesus monkeys (rhesus klotho protein first validated in mice). Low-dose klotho improved memory; a high dose did not. Limitations: Lab or animal research: not evidence of a human effect or dose. [Source](https://pubmed.ncbi.nlm.nih.gov/37400721/) 2. Klotho protein supplementation reduces blood pressure and renal hypertrophy in db/db mice, a model of type 2 diabetes. Acta Physiol (Oxf). 2019. 2018. Preclinical: animal or lab study. Population: db/db mice, a model of type 2 diabetes. Lower kidney weight, systolic blood pressure and albuminuria; no change in body weight. Limitations: Lab or animal research: not evidence of a human effect or dose. [Source](https://pubmed.ncbi.nlm.nih.gov/30251773/) 3. NCT07285629 — Safety and Efficacy of Klotho and Follistatin Gene Therapy. Human study (early or uncontrolled). Population: Healthy adult volunteers (n=14). Safety, cognitive and health measures before and after; no results posted. Research on a related compound, not this one. Limitations: Studied an analog, not Klotho itself [Source](https://clinicaltrials.gov/study/NCT07285629) ### Registered trials - [NCT07285629](https://clinicaltrials.gov/study/NCT07285629) ## Safety Side effects: Unknown for unregulated vials. Risks: Not a characterized peptide drug; Product identity varies. Human safety basis: No controlled human safety data Key limitations: No established human dosage.; No controlled human trial results in the reviewed sources.; Not approved by the FDA for any use.. ## Regulatory status Klotho is not an FDA-approved product. It is sold for laboratory research and has no approved medical use. - FDA status: Not Approved - Availability: Research-Only ## Frequently asked questions ### What is Klotho? Transmembrane and soluble anti-aging protein that is an FGF23 co-receptor. Shop “Klotho” vials are not an FDA-approved drug and are often fragments or poorly characterized proteins. ### How does Klotho work? Alpha-Klotho is a single-pass transmembrane protein expressed mainly in kidney and choroid plexus. Membrane-bound Klotho functions as an obligate co-receptor: FGF23 binds FGF receptors with low affinity alone, and Klotho is required to form a high-affinity complex, which is how FGF23 regulates phosphate excretion and vitamin D metabolism. ### Is Klotho FDA approved? No. Klotho is not approved by the FDA for any indication and is categorised as research-only. It has not been reviewed for safety or efficacy as a medicine, and published research should be read as investigation rather than established use. ### What peptides are similar to Klotho? Compounds most often compared with Klotho include Epitalon, Pinealon, FOXO4-DRI and NAD+ (Nicotinamide Adenine Dinucleotide). They are grouped by shared mechanism or research area rather than by equivalence, and their regulatory status and evidence base differ. ## References - [Klotho gene polymorphisms are associated with healthy aging and longevity: Evidence from a meta-analysis — Mech Ageing Dev, 2019](https://pubmed.ncbi.nlm.nih.gov/30633899/) - [Klotho antiaging protein: molecular mechanisms and therapeutic potential in diseases — Mol Biomed, 2025](https://pubmed.ncbi.nlm.nih.gov/40119098/) - [Anti-Inflammatory Role of the Klotho Protein and Relevance to Aging — Cells, 2024](https://pubmed.ncbi.nlm.nih.gov/39272986/) - [The current and emerging Klotho-enhancement strategies — Biochem Biophys Res Commun, 2024](https://pubmed.ncbi.nlm.nih.gov/38091839/) - [Interaction of Klotho and sirtuins — Exp Gerontol, 2023](https://pubmed.ncbi.nlm.nih.gov/37804921/)