In tumor-induced osteomalacia, excessive production of factors such as FGF 23 and frizzled-related protein-4 is associated with inability of endogenous proteolytic enzymes to degrade these individual substances, with resultant hyperphosphaturia, hypophosphatemia, and rickets. In XLH, mutant PHEX/phex (phosphate-regulating gene with homology to endopeptidases located on the X-chromosome) activity prevents degradation of a phosphaturic factor. In autosomal-dominant hypophosphatemic rickets, a mutant form of FGF 23 that is resistant to proteolytic degradation causes increased renal phosphate losses and hypophosphatemia.