CYP39A1 is a cytochrome P450 monooxygenase primarily involved in neural cholesterol clearance through bile acid synthesis 12. It catalyzes 7-alpha hydroxylation of (24S)-hydroxycholesterol, a neural oxysterol metabolized to bile acids in the liver, using molecular oxygen and NADPH via cytochrome P450 reductase 12. Beyond canonical oxysterol metabolism, CYP39A1 exhibits tumor-suppressive functions. In hepatocellular carcinoma (HCC), CYP39A1 expression is dramatically reduced in >90% of patients, and its restoration blocks tumor formation in both sexes through a non-enzymatic mechanism involving c-Myc inhibition 3. Similarly, in colorectal cancer, CYP39A1 knockdown reduces tumor cell migration, invasion, angiogenesis, and lymphangiogenesis 4. Downregulation correlates with poor prognosis across cancers 56. Genetically, loss-of-function CYP39A1 variants associate with significant ocular pathology. The G204E variant confers 7.1-fold increased blindness risk and 5.1-fold increased exfoliation glaucoma risk in exfoliation syndrome patients 7. Rare damaging CYP39A1 variants show 3.55-fold association with exfoliation syndrome development 8, with 34 of 42 identified variants demonstrating >78% enzymatic activity reduction. CYP39A1 also influences busulfan clearance in pediatric stem cell transplantation, explaining 17% of pharmacokinetic variability when combined with GSTA1 9.