Urate transporter 1 (URAT1) (URAT1)

Urate transporter 1 (URAT1), also known as SLC22A12, is a membrane transporter protein primarily expressed in the renal proximal tubule. It mediates the reabsorption of filtered urate (uric acid) back into the bloodstream by facilitating anion exchange—most notably with lactate and other organic anions—across the apical membrane of epithelial cells[1][2][3][4][7]. The URAT1 protein consists of multiple transmembrane domains and demonstrates high substrate specificity for urate. Genetic variations or dysfunction in URAT1 can lead to altered uric acid levels, contributing to gout, nephrolithiasis, or hypouricemia. URAT1 is a clinically validated therapeutic target for gout, with several approved drugs specifically inhibiting its function to promote uric acid excretion and decrease hyperuricemia. Recent cryo-EM studies have revealed its detailed structure, mechanisms of substrate recognition, and drug inhibition modes, facilitating rational drug design[1][4][7].

Other names

SLC22A12Solute carrier family 22 member 12Human urate transporter 1

Inhibition of URAT1 reduces renal reabsorption of urate, increasing urinary uric acid excretion and lowering serum urate concentrations[1][2][4][7]. Competitive antagonism at the urate binding site (for most drugs listed above)[1].