CYP26

CYP26 enzymes are cytochrome P450 retinoic acid hydroxylases that regulate intracellular all-trans-retinoic acid (atRA) concentrations and maintain retinoid homeostasis through rapid metabolic clearance of active retinoids^[1][2]. The CYP26 family comprises CYP26A1, CYP26B1, and CYP26C1, which efficiently metabolize atRA and related retinoid isomers, thereby controlling retinoic acid receptor signaling during development and in adult tissues^[2][3]. Mechanistically, CYP26-mediated catabolism generates retinoic acid gradients that shape tissue-specific gene expression patterns and protect selected tissues from excessive retinoid signaling during embryogenesis^[4][5]. Disruption of CYP26-dependent retinoic acid homeostasis has been linked to developmental abnormalities, altered neuronal retinoid signaling, and pathological changes associated with cancer and other retinoid-responsive diseases^[5][6][7]. Compared with related isoforms, CYP26A1 is the predominant hepatic atRA hydroxylase with higher catalytic capacity, whereas CYP26B1 exhibits higher substrate affinity and primarily regulates extrahepatic retinoid clearance^[8][9]. CYP26C1 also contributes to retinoid metabolism but remains less extensively characterized than CYP26A1 and CYP26B1^[2][3]. For experimental applications, selective and dual CYP26 inhibitors, including retinoic acid metabolism blocking agents (RAMBAs) such as talarozole and DX314, increase endogenous atRA exposure and are widely used to investigate tissue-specific retinoid signaling and therapeutic responses in dermatological and cancer-related models^[7][10][11].