klotho

Klotho is a naturally occurring human protein encoded by the KL gene and exists in three subfamilies: α-klotho (alpha), β-klotho (beta), and γ-klotho (gamma). The term "klotho" typically refers to α-klotho unless otherwise specified. Klotho functions as a type-I single-pass transmembrane protein with both membrane-bound and soluble forms. It acts as a co-receptor for fibroblast growth factors—α‑klotho for FGF23 and β‑klotho for FGF19/FGF21—regulating phosphate and vitamin D metabolism. Klotho modulates several molecular pathways including Wnt signaling, hypoxia-inducible factor pathway, insulin/insulin-like growth factor 1 signaling, and exerts antioxidative effects. Its deficiency is associated with accelerated aging phenotypes such as cognitive impairment, osteoporosis, arteriosclerosis, chronic kidney disease progression, cardiovascular diseases (including coronary artery disease and left ventricular hypertrophy), diabetes risk increase, muscle atrophy/frailty in aging populations as well as neurodegenerative disorders like Alzheimer’s disease. Overexpression or supplementation of klotho has been shown in animal models to extend lifespan and improve physical/cognitive health[1][3][4][5].

Other names

α-klothobeta-klothoγ-klothoalpha-klothogamma-klotho