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ABCG2 is a high-capacity urate exporter. Two frequent variants, Q126X and Q141K are a nonfunctional and half-functional variant, respectively. The estimated ABCG2 dysfunction based on the combination of Q126X and Q141K haplotype raises gout/hyperuricemia risk. ABCG2 dysfunction accounts for about 80% of gouty patients. Severe ABCG2 dysfunction particularly increased the risk of early-onset gout. Hyperuricemia has been clinically classified into urate 'overproduction type' and/or 'underexcretion type' based solely on renal urate excretion, without considering an extra-renal pathway. A major cause of'overproduction' hyperuricemia is not true overproduction of urate but rather'extra-renal urate underexcretion' by common ABCG2 dysfunction. As ABCG2 dysfunction is a main cause of gout, ABCG2 research will provide a new approach for prevention and treatment of gout.

An inhibitor of xanthine dehydrogenase (XDH), allopurinol, and uricosuric agents, probenecid and benzbromarone, have been used for more than 20 years in the treatment of hyperuricemia and gout. However, they are inconvenient in some situations. With regard to allopurinol, the dosage reduction is recommended in patients with renal insufficiency for preventing from rare adverse effect, bone marrow depression. Benzbromarone also has quite rare adverse effect, fulminant hepatitis. Recently several new therapies have been developed such as new XDH inhibitors urate transporter (URAT) 1 inhibitor, and a modified recombinant uricase. The dosage reduction of the new XDH inhibitors, febuxostat and FYX-051, is not necessary in patients with renal insufficiency because renal excretion is not main excretory pathway. JTT-552 is a first medicine targeting on URAT1. Polyethylene glycol (PEG) conjugation with recombinant uricase sufficiently reduces the immunogenicity to permit repeated dosing and the clinical trials are ongoing for patients with treatment-failure gout and hyperuricemia.