Klotho–fibroblast growth factor 23 endocrine axis (No standard abbreviation exists for the axis as a whole, but the components are commonly abbreviated as FGF23 (for fibroblast growth factor 23) and Klotho (for the α-Klotho protein))

The Klotho–fibroblast growth factor 23 (FGF23) endocrine axis is a critical physiological regulatory network that maintains phosphate and vitamin D homeostasis in mammals. FGF23, produced by bone, acts through fibroblast growth factor receptors (primarily FGFR1c) in the kidney and parathyroid gland, with α-Klotho protein functioning as an essential coreceptor to confer high affinity and specificity. This axis promotes renal phosphate excretion and suppresses vitamin D activation, counter-regulating the actions of parathyroid hormone and vitamin D. Disruption or dysregulation of this network leads to profound disturbances in mineral metabolism, contributing to chronic kidney disease, accelerated vascular calcification, premature aging syndromes, and increased cardiovascular risk. While the axis itself is not a single molecular drug target, its main components are targets of both mechanistic and therapeutic interest, and circulating levels of FGF23 and Klotho are emerging as important biomarkers in kidney and metabolic diseases.

Other names

FGF23–Klotho axisFGF23/α-Klotho endocrine axisFGF23–Klotho pathwayBone–kidney endocrine axisFGF23/Klotho system

For anti-FGF23 antibody (burosumab): FGF23 inhibition increases renal phosphate reabsorption and serum phosphate. Modulators of Vitamin D or PTH indirectly affect axis signaling. Potential for Klotho upregulation or mimetics in experimental therapies