CYP2A6 is a polymorphic cytochrome P450 enzyme that plays a critical role in xenobiotic metabolism, serving as the major nicotine C-oxidase responsible for nicotine metabolism to cotinine in humans 1. The enzyme exhibits high coumarin 7-hydroxylase activity and metabolizes various substances including anti-cancer drugs cyclophosphamide and ifosphamide, and can activate procarcinogens such as aflatoxin B1 1. CYP2A6 also metabolizes polychlorinated biphenyls (PCBs), producing hydroxylated metabolites that may contribute to toxicity and carcinogenesis 23. The enzyme demonstrates significant genetic polymorphism with multiple allelic variants including deletion alleles (CYP2A6*4A, CYP2A6*4D) and point mutations (CYP2A6*7, CYP2A6*10) that substantially alter enzymatic activity 45. Genetic variations in CYP2A6 have important clinical implications, affecting nicotine metabolism rates and potentially influencing smoking behavior and tobacco-related disease risk 6. The enzyme shows complex interactions with other cytochrome P450 enzymes like CYP2B6, which can compensate for reduced CYP2A6 activity in nicotine metabolism 7. These pharmacogenetic variations make CYP2A6 an important consideration for personalized medicine approaches in smoking cessation and drug metabolism assessment 8.