Abstract
α-Klotho was first identified as an aging gene and was later shown to be a regulator of mineral metabolism. Then, α-Klotho was reported to function as an obligate coreceptor for fibroblast growth factor 23 (FGF23). Phosphrus regulation of FGF23/Klotho axis is slow. On the other hand, α-Klotho is a key player that integrates "a multi-step regulatory system of calcium homeostasis" that rapidly adjusts the extracellular calcium concentration. In addition to its membrane-bound function as a co-receptor for fibroblast growth factor 23, soluble Klotho exerts effects as a circulating substance in plasma and urine. The Klotho protein not only serves as a coreceptor for FGF23, but also functions as a humoral factor.
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