This study not only reveals a new KEAP1‐independent mechanism of NRF2 protein stability via disruption of NRF2/DUB3 complex by AMBRA1 in intestinal epithelial cells, but also highlights USP7 as a deubiquitinase of AMBRA1 in response to oxidative stress and the therapeutic potential of targeting USP7‐AMBRA1 axis for inflammatory bowel disease treatment. The gene discussed is AMBRA1; the disease is inflammatory bowel disease.