CYP2C9 is a hepatic cytochrome P450 monooxygenase that catalyzes the metabolism of endogenous substrates and xenobiotics. Mechanistically, it inserts one oxygen atom into substrates while reducing the second to water, utilizing electrons from NADPH via cytochrome P450 reductase 1. The enzyme performs diverse oxidative transformations including epoxidation of polyunsaturated fatty acids, cholesterol hydroxylation to 25-hydroxycholesterol for cholesterol homeostasis regulation, and metabolizes drugs such as warfarin and tolbutamide 2. CYP2C9 genetic polymorphisms significantly impact drug pharmacokinetics and disease risk. Common variants like CYP2C9*2 and *3 show reduced catalytic activity, requiring dose adjustments for warfarin and other substrates 3. Gene polymorphisms affect inter-individual variability in drug metabolism, with 28 of 38 tested variants exhibiting decreased clearance for azilsartan, while pathogenic missense variants compromise protein stability 45. Environmental exposures can modulate CYP2C9 expression; bisphenol A upregulates the enzyme via estrogen receptor α, potentially affecting drug metabolism homeostasis 6. Drug-drug-gene interactions further complicate therapy, as inhibitors like pterostilbene can suppress CYP2C9 activity, increasing substrate exposure 7. These findings underscore the importance of pharmacogenetic testing for precision medicine approaches.