Elevated levels of FGF-23 are associated with several hereditary and acquired hypophosphatemic disorders including X-linked hypophosphatemic rickets (Hyp mice homolog)—caused by inactivating mutations of Phex (5–7)—autosomal recessive hypophosphatemic rickets 1—caused by inactivating mutations of Dmp1 (5, 7)—ARHR2—caused by inactivating mutations in Enpp1 (6–10)—and Raine syndrome—caused by inactivating mutations in FAM20C (11, 12). This evidence concerns the gene ENPP1 and lethal osteosclerotic bone dysplasia.