In this study, we overcame the technical difficulties in the expression and purification of the native human URAT1 and used cryo-electron microscopy (cryo-EM) to unveil the structures of URAT1 bound with four anti-gout drugs (dotinurad, benzbromarone, lesinurad, and verinurad), revealing their binding and inhibition mechanisms. This evidence concerns the gene SLC22A12 and gout.