Aldo-keto reductase 1B: Much learned, much more to do

The aldo-keto reductase 1B (AKR1B) subfamily was initially known for its association with the pathogenesis of secondary diabetic complications such as retinopathy, neuropathy, nephropathy, and cataracts. Unfortunately, over the past few decades, all drug development efforts targeting this family have failed for one reason or another. Recently, a growing body of evidence showing the deep involvement of AKR1B in metabolic reprogramming and production of signaling metabolites has led to a re-evaluation of their role in the pathogenesis of several immunometabolism-related diseases, such as gastrointestinal diseases, psoriasis, congenital disorders of glycosylation, carcinogenesis, even progression, and acquired chemoresistance. Therefore, in this review, we will summarize the current knowledge of AKR1B, highlighting their potential function in regulating immune cell function and then inflammatory complications. We will also explore how discovering this new insight into this old enzyme is essential for envisioning potential therapeutic strategies to prevent or treat inflammatory diseases.