Initial mouse models examining global deletion of Cyp27b1, [1α(OH)ase−/− mice], produced a phenocopy of the congenital human disease vitamin D–dependent rickets type 1A (VDDRIA), also known as pseudovitamin D deficiency rickets (PDDR).(3, 4) The major source of circulating 1,25(OH)2D is the renal 1α(OH)ase enzyme, which is tightly upregulated by parathyroid hormone (PTH) and hypophosphatemia, and downregulated by the phosphaturic hormone fibroblast growth factor 23 (FGF23), by hypercalcemia, and by 1,25(OH)2D itself. This evidence concerns the gene FGF23 and hypophosphatemia.