CYP26A1 is a cytochrome P450 monooxygenase that serves as the primary hepatic enzyme responsible for retinoic acid (RA) catabolism and homeostasis 1. The enzyme catalyzes the hydroxylation of all-trans-retinoic acid (atRA) primarily at C-4 and C-18 positions, producing metabolites including 4-OH-RA, 4-oxo-RA, 16-OH-RA, and 18-OH-RA 1. CYP26A1 also metabolizes other RA isomers including 9-cis-RA and 13-cis-RA 1. The enzyme's expression is biphasic and spatiotemporally regulated, playing critical developmental roles including human macular formation where two waves of CYP26A1-mediated RA suppression modulate cell cycle exit and cone subtype specification 2. In colorectal cancer, CYP26A1 functions as an oncogene that degrades ATRA to less bioactive retinoids, contributing to ATRA resistance and promoting tumor progression 34. The enzyme is upregulated in colorectal cancer tissues and creates an immunosuppressive tumor microenvironment 4. CYP26A1's promoter serves as a sensitive biomarker for RAR-mediated retinoid activity and can be used to assess retinoid bioavailability in various tissues 5. The enzyme represents a potential therapeutic target, as CYP26A1 inhibitors can enhance ATRA therapeutic efficacy in cancer treatment 3.