SLC22A12 encodes URAT1 (urate transporter 1), an electroneutral antiporter primarily responsible for uric acid reabsorption in the kidney proximal tubules 1. URAT1 functions by translocating urate across the apical membrane in exchange for monovalent organic anions (such as lactate and nicotinate) or inorganic anions (including chloride, bromide, iodide, and nitrate), thereby maintaining blood uric acid levels 2. Structural studies reveal that urate binds in a phenylalanine-rich pocket and engages gating residues to drive the transport cycle, with pyrazinoate interacting at three distinct sites within the transporter 2. The transporter's activity is regulated by phosphorylation at Thr408, which is stimulated by hyperinsulinemia via AKT signaling and by high salt intake through SGK1, linking metabolic conditions to uric acid homeostasis 3. Loss-of-function mutations in SLC22A12 cause hereditary renal hypouricemia type 1, characterized by excessive uric acid excretion and serum uric acid levels below 2mg/dL 45. The gene shows significant genetic variation affecting hyperuricemia susceptibility, with certain polymorphisms serving as risk or protective factors 6. URAT1 represents a major therapeutic target for gout treatment, with drugs like lesinurad, verinurad, and dotinurad acting as competitive inhibitors 2.