Aldose reductase (AR) is an NADPH-dependent enzyme that was first identified by its ability to reduce glucose to sorbitol. The deduced 316-amino acid AKR1B10 protein shares 71% amino acid identity with AR. Northern blot analysis revealed that AKR1B10 is overexpressed in 54% of HCCs, while AR is overexpressed in 29% of HCCs. Northern blot analysis of normal tissues showed that unlike the ubiquitously expressed AR, AKR1B10 is expressed most abundantly in small intestine and colon, with lower levels in liver, thymus, prostate, testis, and skeletal muscle. AR and ARL1 reduce a similar spectrum of aromatic and aliphatic aldehyde substrates.Highest expression of AKR1B10 in adrenal gland, with modest expression in stomach, placenta, small intestine, and pancreas, and lower expression in all other tissues tested.