The primary function of vitamin D in higher vertebrates is to regulate mineral homeostasis through direct actions on intestinal calcium (Ca) and phosphate (P) absorption, bone mineral resorption, and renal mineral reabsorption. Vitamin D itself is inactive and must undergo sequential modification via two specific chemical reactions, first in the liver to 25 (OH) D3 by the enzyme CYP2R1, and then in the kidney to 1, 25-dihydroxyvitamin D3 [1, 25 (OH) 2D3 or calcitriol] by the tightly regulated enzyme CYP27B1 (1). Calcitriol, whose level is also modulated via renal CYP24A1–mediated degradation, is then secreted into the blood as an active endocrine hormone and delivered to distant target tissues.