p62/SQSTM1 positively regulated the DNA binding activity of Nrf2 by physical association with Keap-1 and activates its transcriptional activity on ARE. Therefore, reduction of p62/SQSTM1 in hepatocytes, regardless of the existence of steatosis, lowered the expression of anti-oxidant molecules (catalase, MnSOD, Ref-1, HO-1, TRX, and GPx) by increasing Keap-1/Nrf2 binding (i.e., decreasing ARE activity), making the hepatocytes/liver susceptible to harmful OS. The gene discussed is HMOX1; the disease is steatosis.