Urate anion transporter 1 (URAT1) (URAT1)

Solute carrier family 22 member 12 (URAT1) is a transmembrane protein primarily expressed on the apical membrane of renal proximal tubular cells, where it plays a pivotal role in urate homeostasis [1.2.1, 1.4.4]. It functions as an anion exchanger, mediating the reabsorption of approximately 90% of filtered urate from the urine back into the bloodstream [1.1.3, 1.4.1]. Overactivity or high expression of URAT1 is a major contributor to hyperuricemia and the subsequent development of gout, a painful inflammatory arthritis caused by the deposition of monosodium urate crystals in joints [1.1.2, 1.3.1]. Conversely, loss-of-function mutations in the SLC22A12 gene result in renal hypouricemia, characterized by low serum urate levels and an increased risk of exercise-induced acute kidney injury [1.4.1, 1.4.3]. URAT1 is a primary therapeutic target for uricosuric drugs, such as lesinurad and benzbromarone, which inhibit the transporter to promote uric acid excretion [1.1.2, 1.3.2]. These inhibitors typically work by stabilizing the transporter in an inward-facing conformation, effectively blocking the urate-binding site [1.3.1, 1.3.3]. While effective at lowering serum urate, these therapies require careful monitoring due to potential safety concerns, including nephrolithiasis and acute renal impairment resulting from high concentrations of urate in the renal tubules [1.1.1, 1.3.4].

Other names

SLC22A12OAT4LRSTRenal-Specific TransporterHURAT1UATUrate Anion Transporter 1Urate Anion Exchanger 1Solute carrier family 22 member 12

URAT1 inhibitors act as uricosuric agents by blocking the reabsorption of uric acid in the renal proximal tubules. Recent structural studies indicate that these drugs, such as lesinurad and benzbromarone, bind to the central cavity of the transporter and stabilize it in an inward-facing conformation, preventing the conformational transitions necessary for urate transport [1.3.1, 1.3.2, 1.3.3]. This leads to increased urinary excretion of uric acid and a subsequent reduction in serum urate levels [1.1.2, 1.2.1].