 Gene mutations in PHEX prevent it from correctly regulating fibroblast growth factor 23.The resulting overactivity of FGF-23 reduces vitamin D 1α-hydroxylation and phosphate reabsorption by the kidneys, leading to hypophosphatemia and the related features of hereditary hypophosphatemic rickets.Also in XLH, where PHEX enzymatic activity is absent or reduced, osteopontin—a mineralization-inhibiting secreted substrate protein found in the extracellular matrix of bone—accumulates in bone (and teeth) to contribute to the osteomalacia (and odontomalacia) as shown in the mouse homolog (Hyp) of XLH and in XLH patients.