Inactivating mutations in the phosphate-regulating endopeptidase homolog X-linked (PHEX) gene lead to increased FGF23 secretion from osteocytes and osteoblasts, inducing renal phosphate wasting, hypophosphatemia, and impairing the endogenous production of active vitamin D [1,25(OH)2vitamin D] via the inhibition of 1α-hydroxylase and the activation of 24-hydroxylase (2). The gene discussed is PHEX; the disease is hypophosphatemia.