While it is well documented that CYP2E1 contributes to oxidative stress pathways in ALD and DILI, many reports have also demonstrated the critical role of CYP2E1 in MASLD through the production of ROS and LPOs; this may represent the second hit in the progression of steatosis to MASH [26, 41, 68, 178, 244]. This evidence concerns the gene CYP2E1 and metabolic dysfunction-associated steatotic liver disease.