CYP2S1 is a cytochrome P450 monooxygenase primarily expressed in epithelial tissues of organs exposed to xenobiotics, including the respiratory, gastrointestinal, and urinary tracts, as well as skin 1. The enzyme metabolizes both endogenous lipid mediators and exogenous compounds. Endogenously, CYP2S1 catalyzes oxidative metabolism of all-trans-retinoic acid in epidermis and displays peroxidase and isomerase activities toward eicosanoids, including prostaglandin H2 and hydroperoxyeicosatetraenoates, producing mediators such as malondialdehyde that can act as a DNA-damaging agent 2. For xenobiotic metabolism, CYP2S1 is inducible by dioxin via the aryl hydrocarbon receptor and metabolizes naphthalene and other polycyclic aromatic hydrocarbons 1. Recent evidence suggests CYP2S1 modulates intestinal homeostasis by regulating the metabolome and microbiome through aryl hydrocarbon receptor signaling; Cyp2s1-deficient mice show reduced expression in inflammatory bowel disease 3. Genetic polymorphisms affecting CYP2S1 function have been documented across populations, and altered CYP2S1 methylation is associated with high-altitude pulmonary edema and psoriasis, implicating the enzyme in inflammatory and proliferative skin diseases 45.