SULT1C3 (sulfotransferase family 1C member 3) is a poorly characterized phase II xenobiotic-metabolizing enzyme with restricted substrate specificity 1. Unlike other human SULTs, SULT1C3 displays negligible activity toward common substrates like 4-nitrophenol and paracetamol 2, instead preferring large benzylic alcohols derived from polycyclic hydrocarbons and chlorinated compounds 2. The enzyme exists as multiple splice variants (SULT1C3a and SULT1C3d) with distinct catalytic properties; SULT1C3a shows strict substrate specificity toward hydroxyl-chlorinated biphenyls, while SULT1C3d exhibits broader substrate specificity including bile acids and thyroid hormones 1. SULT1C3 is expressed in human intestine and colorectal cells 3, where its transcription is regulated by peroxisome proliferator-activated receptors (PPARα, δ, γ), suggesting involvement in intestinal growth, differentiation, and metabolism 4. Clinically, SULT1C3 exhibits the highest affinity for tolvaptan sulfation among SULT isoforms and significantly enhances tolvaptan cytotoxicity 5, potentially contributing to drug-induced liver injury. Notably, SULT1C3 shows no detectable activity toward nevirapine metabolites 6, indicating selective substrate recognition. The gene appears unique to primates 1, with physiological substrates remaining largely unidentified.