αKlotho: FGF23 coreceptor and FGF23-regulating hormone

Abstract

Low levels of phosphate can disrupt bone ossification and predispose to fractures. FGF23 is one of the major determinants of phosphate homeostasis, acting to increase urinary phosphate excretion. However, the regulation of FGF23 is incompletely understood. In this issue of the JCI, Smith et al. show that the cleaved form of αKlotho, the membrane-bound form of which is an FGF23 coreceptor, serves as a novel endocrine regulator of phosphate homeostasis, capable of inducing FGF23 production in osteocytes.