CYP24A1 is a mitochondrial cytochrome P450 monooxygenase essential for vitamin D catabolism and calcium homeostasis. It catalyzes the inactivation of both 25-hydroxyvitamin D (calcidiol) and the active hormone 1,25-dihydroxyvitamin D (calcitriol) through C24- and C23-oxidation pathways, ultimately producing calcitroic acid and 25(OH)D3-26,23-lactone for excretion 1. The enzyme uses molecular oxygen to hydroxylate vitamin D metabolites, with electrons supplied by NADPH via the FDXR/FDX1 electron transport system. Kidney CYP24A1 regulates systemic vitamin D levels, while intestinal CYP24A1 exerts tissue-specific effects independent of systemic regulation 1. In chr20 kidney disease, elevated phosphate and FGF-23 increase CYP24A1 expression, reducing vitamin D status and contributing to renal osteodystrophy 2. Loss-of-function mutations in CYP24A1 cause idiopathic infantile hypercalcemia, characterized by PTH-independent hypercalcemia, hypercalciuria, and nephrocalcinosis; even monoallelic variants can cause symptomatic disease 3. Additionally, CYP24A1 polymorphisms associate with cancer susceptibility, with rs4809960 showing reduced cancer risk in multiple populations 4.