CYP2A13 is a lung-specific cytochrome P450 enzyme that catalyzes the metabolic activation of tobacco-specific carcinogens and environmental toxins. Structurally, CYP2A13 exhibits coumarin 7-hydroxylase activity 1 and possesses broad substrate specificity, metabolizing nicotine, cotinine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and aflatoxin B1 2. Notably, CYP2A13 catalyzes phenacetin O-deethylation with higher intrinsic clearance than the hepatic CYP1A2 enzyme 3. Mechanistically, CYP2A13 is predominantly expressed in epithelial cells of human bronchi and trachea but rarely in alveolar cells 4, positioning it for localized bioactivation of inhaled carcinogens. In vivo studies demonstrate that CYP2A13 mediates naphthalene-induced respiratory tract toxicity through bioactivation 5. Disease relevance is substantial: CYP2A13-catalyzed metabolic activation of NNK in airways may critically contribute to smoking-related bronchogenic lung cancer development 2. Additionally, CYP2A13 genetic variants encoding inactive enzyme appear protective against pancreatic cancer 6. Clinically, CYP2A13 represents a therapeutic target; flavonoid inhibitors show potent suppression of CYP2A13 activity 7, suggesting potential utility in smoking cessation interventions.