Cyp24a1−/− mice exhibited increased 1,25(OH)2D levels, hypercalcemia, hypercalciuria, and an intramembranous bone lesion that healed when a double Cyp24a1/Vdr null mouse was generated, indicating that the elevated 1,25(OH)2D, acting through Vdr, was responsible for the bone defect.(5) These observations in Cyp24a1−/− mice preceded observations in humans demonstrating that inactivating mutations in CYP24A1 are a cause of idiopathic infantile hypercalcemia,(11) as well as a syndrome of intermittent hypercalcemia, hypercalciuria, nephrocalcinosis, and kidney stones, in some adults.(12). This evidence concerns the gene CYP24A1 and nephrocalcinosis.