Proposed models of urate transport in the proximal tubule suggest an initial uptake of uric acid from the filtrate by URAT1, coupled to organic acid transporters. GLUT9, in two different isoforms, allows for basolateral exit of urate from the proximal tubule and regulation of urate entry/exit at the apical membrane. Finally, in the late proximal tubule there are transporter proteins mediating uric acid secretion. As uric acid excretion is mediated through molecular transporters, certain drugs such as fenofibrate, valproic acid, trimethoprim and losartan may be used to manipulate these processes, thus allowing manipulation of serum uric acid levels. In humans, genetic defects in the activity of xanthine oxidase or an acquired defect in liver enzyme function or renal uric acid handling may result in hypouricaemia. Acquired hypouricaemia may be seen in a number of clinical disorders, including Fanconi syndrome, type 1 and type 2 diabetes mellitus, thyrotoxicosis, pseudohypoparathyroidism type 1b, pseudoaldosteronism due to licorice ingestion, distal renal tubular acidosis, obstructive jaundice and severe acute respiratory syndrome. Idiopathic renal hypouricaemia is an inherited form of hypouricaemia that is characterized by excessive urinary wasting of uric acid leading to an increased clearance of uric acid. The majority of Torin 1 patients are asymptomatic, but some may present with uric acid nephrolithiasis or acute kidney injury following severe exercise. In 2002, Enomoto et al. reported that mutations in gene SLC22A12 encoding the URAT1 transporter were responsible for most cases of idiopathic renal hypouricaemia. Recently Anzai et al. found mutations in SLC2A9, encoding GLUT9, in patients with severe renal hypouricaemia. It is noteworthy that reports of idiopathic renal hypouricaemia secondary to mutations in uric acid transporters URAT1 and GLUT9 were initially reported from Japan, Korea and China. More recently, three Jewish Israeli families of Iraqi origin have been reported to have renal hypouricaemia, with a common mutation in SLC22A12. Inactivating mutations in SLC22A12 have not yet, to our knowledge, been reported in a Caucasian population. The typical presentation of idiopathic renal hypouricaemia is that of exercise induced acute kidney injury with a preceding history of loin pain with nausea and vomiting for several hours after physical exercise. The exact mechanism of renal damage is unclear, but may relate to damage from oxygen free radicals. In contrast to this dramatic presentation, most patients are well with no overt clinical symptoms, although renal stones and hematuria may be presenting symptoms and signs. Here we present data from Skopje and Newcastle upon Tyne where we have investigated the underlying genetic cause of hypouricaemia in patients of European descent. We present mutations in SLC22A12 encoding URAT1 alongside their clinical, biochemical and functional characterization. This data highlights the importance of renal urate transporters in determining serum urate concentrations. Idiopathic renal hypouricaemia is a disorder that has been characterized previously in patients from Far Eastern countries including Japan, Korea and China.