CYP51A1 (sterol 14α-demethylase) is a highly conserved cytochrome P450 enzyme essential for cholesterol biosynthesis 1. It catalyzes the three-step oxidative demethylation of lanosterol and 24,25-dihydrolanosterol, converting them to intermediates in the cholesterol synthesis pathway 2. Beyond its canonical metabolic role, CYP51A1 has emerged as a critical regulator of multiple forms of regulated cell death. In ferroptosis, CYP51A1 functions as a ferroptosis suppressor by maintaining 7-dehydrocholesterol (7-DHC) levels, which shields cell membranes from phospholipid autoxidation 3. In pancreatic cancer, CYP51A1 drives resistance to pH-dependent cell death by preventing cholesterol accumulation in lysosomes and enabling lysosomal proton efflux 4. CYP51A1 shows exceptionally low nucleotide variability in humans, indicating strong evolutionary conservation and selection pressure 5. Disease associations have expanded beyond traditional metabolic disorders to include cancer, neurodegeneration, and cerebral palsy, where CYP51A1 variants were identified as plausible candidate genes 6. These findings demonstrate that CYP51A1 integrates metabolic homeostasis with cell fate control, positioning it as a promising therapeutic target across diverse pathological contexts 2.