CYP2F1 is a cytochrome P450 enzyme with highly tissue-selective expression, showing highest activity in lung with minimal hepatic expression 1. The enzyme functions primarily in the bioactivation of pulmonary-selective toxicants through oxidative metabolism. CYP2F1 efficiently catalyzes the dehydrogenation of 3-methylindole to its reactive electrophilic metabolite 3-methyleneindolenine, demonstrating remarkable selectivity for this bioactivation pathway 2. The enzyme also metabolizes naphthalene through epoxidation, contributing to naphthalene-induced respiratory tract toxicity in humanized mouse models 3. Additionally, CYP2F1 participates in benzene metabolism in human lung cell lines, working alongside CYP2E1 to bioactivate this environmental toxicant 4. The lung-specific expression of CYP2F1 is regulated by Sp1 and Sp3 transcription factors, with four Sp1-dependent promoter elements driving organ-selective transcription 5. A novel lung-specific factor (LSF) has also been identified that controls tissue-specific CYP2F1 expression 1. Unlike its mouse ortholog CYP2F2, human CYP2F1 does not mediate styrene-induced lung toxicity, suggesting species-specific differences in substrate selectivity and toxicological relevance 67.