CYP46A1 (cholesterol 24-hydroxylase) is a cytochrome P450 enzyme critical for brain cholesterol homeostasis. It catalyzes the conversion of cholesterol to 24S-hydroxycholesterol (24-OHC), a brain-specific oxysterol that readily crosses the blood-brain barrier for hepatic elimination 1. This enzyme accounts for approximately 80% of cholesterol removal from the human brain 2. Beyond cholesterol metabolism, CYP46A1 produces oxysterols that activate nuclear receptors and contribute to synaptic function and neurogenesis [UniProt references]. CYP46A1 dysregulation is implicated in multiple neurodegenerative diseases. In Parkinson's disease, elevated CYP46A1 and 24-OHC levels promote α-synuclein pathology through the XBP1-LAG3 axis, while genetic removal of CYP46A1 attenuates neurodegeneration 3. In Alzheimer's disease, cholesterol homeostasis is impaired, with emerging evidence linking CYP46A1 modulation to disease pathophysiology 4. CYP46A1 overexpression shows sex-specific cognitive benefits in females by enhancing estrogen signaling, while impairing memory in males 5. In Huntington's disease, AAV-CYP46A1 delivery restores cholesterol metabolism with neuroprotective effects 6. Additionally, CYP46A1 polymorphisms influence glaucoma risk 7, and the selective CYP46A1 inhibitor soticlestat demonstrates anti-seizure efficacy 2. Both inhibition and activation of CYP46A1 represent therapeutic strategies depending on disease context.