alpha-klotho

alpha-klotho is a single-pass transmembrane protein with a large extracellular region, predominantly expressed in the kidney, certain brain regions, and to a lesser extent in other tissues[1][7]. The primary biological function of alpha-klotho is to act as a co-receptor for fibroblast growth factor 23 (FGF23), forming a high-affinity signaling complex with FGF23 and the fibroblast growth factor receptor 1c (FGFR1c) to regulate phosphate and calcium metabolism[1][5]. Proteolytic cleavage releases the extracellular domain as a soluble form (soluble alpha-klotho, sKLA), which has both FGF23-dependent and independent functions[1]. Alpha-klotho is considered a geroprotective, anti-aging factor, with roles in attenuating oxidative stress, inflammation, and promoting insulin/IGF-1, mTOR, and Wnt signaling pathways[7][8]. Deficiencies in alpha-klotho are associated with accelerated aging phenotypes, cognitive decline, and increased risk for cardiometabolic and neurodegenerative diseases, while overexpression or supplementation is linked to extended lifespan and improved function in animal models[2][7][14]. Despite promising preclinical data, alpha-klotho has not yet advanced into formal clinical trials as a therapeutic drug in humans, though it is under investigation for applications in neurodegeneration, metabolic disease, and renal protection[3][6].

Other names

α-KlothoKlothosKLA (soluble alpha-klotho)