CYP2C18 is a cytochrome P450 monooxygenase involved in retinoid metabolism. The enzyme catalyzes the hydroxylation of all-trans-retinoic acid (atRA) to 4-hydroxyretinoate, modulating atRA signaling and clearance through a mechanism utilizing molecular oxygen and NADPH via cytochrome P450 reductase [UniProt]. The gene contains nine coding exons spanning approximately 55 kb with a canonical TATA box and multiple regulatory elements including glucocorticoid response sequences 1. CYP2C18 mRNA is expressed in all human liver specimens at 7-8-fold lower levels than CYP2C8 and CYP2C9, with marked interindividual variability 2. Despite high mRNA expression, CYP2C18 protein is not detected in human liver in vivo, though recombinant expression in cell lines demonstrates catalytic activity toward tolbutamide 34. The gene exhibits sexually dimorphic regulation, with male-biased expression in transgenic models primarily regulated by androgen-dependent pituitary growth hormone secretion in liver and direct androgen action in kidney 5. CYP2C18 displays distinct substrate binding properties compared to related CYP2C9 and CYP2C19 enzymes, with computational models identifying unique residues in the active site 6. A genetic polymorphism exists in the 5'-flanking region (allele frequency 21.4%), linked to CYP2C19 variants 7. Clinical significance remains limited due to poor hepatic protein expression in humans, though spliced variants with exon 5 deletion have been identified 4.