Invited Review Article

Department of Pharmacology and Toxicology, Kyorin University School of Medicine, 6-20-2, Shinkawa, Mitaka-shi, Tokyo 181-8611, Japan Corresponding author: Naohiko Anzai, M.D., Ph.D. Department of Pharmacology and Toxicology, Kyorin University School of Medicine, 6-20-2, Shinkawa, Mitaka-shi, Tokyo 181-8611, Japan Tel. +81 4224 7551 1 ext. 3452 Fax. +81 4227 9132 1 E-mail: [email protected], [email protected] Abstract Hyperuricemia is associated with an increased risk of developing gout, hypertension, cardiovascular diseases such as myocardial infarction and stroke, and renal diseases such as acute urate nephropathy and nephrolithiasis, despite its beneficial role, e.g. antioxidative activity. The urate transport system of the kidney is an important determinant of the serum urate level, but clarification of its molecular mechanism remains incomplete. In 2002, our group identified URAT1, a kidney-specific urate transporter, leading to the accumulation of information concerning individual molecules involved in urate transport in the kidney. In 2008, we functionally characterized facilitatory glucose transporter family member GLUT9 as a voltage-driven urate efflux transporter URATv1 and analysis of a renal hypouricemia patient with a genetic defect in URATv1/GLUT9 gene SLC2A9 have established the main route of the urate reabsorption pathway, where urate in the urinary lumen is taken up via URAT1 and intracellular urate exits from the cell to the interstitium/blood space via GLUT9. Therapeutics designed to modify urate transport activities of these proteins might be useful in treating pathologies associated with hyperuricemia. In this review, recent findings concerning these molecules are presented.