Alpha-klotho (α-Klotho) (α-Klotho)

Alpha-klotho is a pleiotropic protein primarily expressed in the kidneys, parathyroid glands, and choroid plexus (UniProt P78537). It exists in two forms: a membrane-bound protein that acts as a co-receptor for fibroblast growth factor 23 (FGF23) and a secreted soluble form that functions as a circulating hormone (PubMed: 29385174). Alpha-klotho plays a critical role in regulating mineral metabolism, specifically phosphate and vitamin D levels, and is widely recognized for its potent anti-aging properties (NIH: PMC6471314). Deficiency in Alpha-klotho is associated with accelerated aging, chronic kidney disease, and cardiovascular complications, while its overexpression has been shown to extend lifespan in animal models (PubMed: 16123302). In therapeutic contexts, it is being explored as a treatment for renal failure and neurodegenerative diseases like Alzheimer's (PubMed: 31515470). Its multifaceted mechanism involves the modulation of multiple signaling pathways, including the inhibition of insulin/IGF-1 and Wnt signaling, as well as the regulation of ion channels and transporters (PubMed: 24014971).

Other names

KlothoKLAlpha-klotho protein

Acts as a mandatory co-receptor for fibroblast growth factor 23 (FGF23) to regulate phosphate and vitamin D metabolism. The soluble form functions as a hormone and enzyme, modulating various signaling pathways including IGF-1, Wnt, and TGF-beta1.