ALDH1A1 is a potential novel target for treatment of ADPKD.

Cheng et al. identify aldehyde dehydrogenase 1A1 as a novel risk factor for autosomal dominant polycystic kidney disease, by both activating proliferative pathways and acting as a transcription factor. Targeting aldehyde dehydrogenase 1A1 with disulfiram delays cyst growth in autosomal dominant polycystic kidney disease mice. Combining low-dose disulfiram with anti-programmed death ligand 1 antibody synergistically attenuates cyst progression and improves the immune microenvironment. Although aldehyde dehydrogenase 1A1 upregulation occurs in other kidney diseases and its transcriptional mechanism warrants further study, repurposing aldehyde dehydrogenase 1A1 inhibitors and programmed death ligand 1 blockades may represent a novel strategy for autosomal dominant polycystic kidney disease therapy.