Klotho protein (Klotho (sometimes α-Klotho, for the primary human form))

The Klotho protein is a type I single-pass transmembrane glycoprotein encoded by the KL gene, with three family members in mammals (α-Klotho, β-Klotho, γ-Klotho). The canonical "Klotho" usually refers to α-Klotho, which is highly expressed in the kidney, brain, and parathyroid gland. Klotho can exist as a membrane-bound form (acting as an obligate co-receptor for fibroblast growth factor 23 in phosphate and vitamin D metabolism) or as a soluble form released from the membrane by proteolytic cleavage, acting as an endocrine/pleiotropic factor influencing multiple signaling pathways. Klotho is associated with lifespan regulation, mineral metabolism, resistance to oxidative stress, and inhibition of fibrosis, making it a potential therapeutic target for aging, chronic kidney disease, neurodegenerative disorders, and metabolic bone diseases. Lower Klotho levels are associated with increased risk of age-related pathologies and poorer outcomes in kidney, cardiovascular, and neurological diseases[1][3][5][7].

Other names

α-Klothobeta-Klothogamma-Klotho (denoting the three subfamilies/isoforms)KL proteinKlotho anti-aging protein

Experimental drugs aim to increase Klotho expression, stability, or delivery (e.g., gene therapy, recombinant Klotho protein). Some medications may upregulate or prolong Klotho signaling indirectly via reduction of phosphate, correction of vitamin D, or reduction of oxidative stress[3].