CYP3A5 is a cytochrome P450 monooxygenase that catalyzes the oxidative metabolism of steroid hormones, vitamins, and xenobiotics. The enzyme inserts one oxygen atom into substrates while reducing a second into water, using electrons provided by NADPH via cytochrome P450 reductase. CYP3A5 exhibits high catalytic activity for conversion of 17β-estradiol and estrone to catechol estrogens, and catalyzes 6β-hydroxylation of testosterone, progesterone, and androstenedione. It also catalyzes oxidative conversion of all-trans-retinol to all-trans-retinal, a rate-limiting step in retinoic acid biosynthesis, and further metabolizes all-trans-retinoic acid for hepatic clearance. CYP3A5 metabolizes xenobiotics including the calcium channel blocker nifedipine and immunosuppressant cyclosporine 1. Genetic polymorphisms in CYP3A5, particularly the rs776746 (6986A>G) variant encoding reduced-activity isoforms, show substantial ethnic variation and create inter-individual differences in drug metabolism that can lead to either increased toxicity or reduced therapeutic effects 2. CYP3A5 is the predominant CYP3A form expressed in human lung tissue 3. In clinical contexts, CYP3A5 genotyping is relevant for personalizing immunosuppressant dosing; donor CYP3A5 polymorphisms account for approximately 14.3% of variation in tacrolimus pharmacokinetics in liver transplant patients 4. Recent evidence suggests cannabidiol preferentially inhibits CYP3A5 over CYP3A4, potentially increasing tacrolimus exposure in transplant recipients 5.