Regulation of fibroblast growth factor 23 (FGF23) in health and disease

Fibroblast growth factor 23 (FGF23) is mainly produced in the bone and, upon secretion, forms a complex with a FGF receptor and coreceptor alpha Klotho. FGF23 can exert several endocrine functions, such as inhibiting renal phosphate reabsorption and 1,25-dihydroxyvitamin D3 production. Moreover, it has paracrine activities on several cell types, including neutrophils and hepatocytes. Klotho and Fgf23 deficiencies result in pathologies otherwise encountered in age-associated diseases, mainly as a result of hyperphosphataemia-dependent calcification. FGF23 levels are also perturbed in the plasma of patients with several disorders, including kidney or cardiovascular diseases. Here, we review mechanisms controlling FGF23 production and discuss how FGF23 regulation is perturbed in disease.