Dysregulation of xanthine oxidoreductase (XOD), the enzyme that catalyzes the endogenous production of uric acid primarily in the liver, and urate transporters that reabsorb urate in renal proximal tubules and secrete urate in renal tubules and the intestine, is the major cause of hyperuricemia, along with variability in the genes encoding these proteins. The gene discussed is XDH; the disease is hyperuricemia.