CYP27B1 and Hypercalcemia: Systemic levels of 1,25-D3 are controlled by the synthesizing enzyme CYP27B1 and the catabolizing enzyme 1,25-dihydroxyvitamin D 24-hydroxylase (CYP24A1) in the kidneys.3 To avoid hypercalcemia induced by excessively high blood levels of 1,25-D3, 1,25-D3 provides feedback inhibition of CYP27B1 expression and coordinately upregulates the expression of CYP24A1.4 The main endocrine function of 1,25-D3 is the modulation of calcium and phosphate homeostasis and bone mineralization.5