PNPLA8 mediates the lipophagy driven by sterol-regulatory element binding protein 2 (SREBP-2) through its dynamic interaction with LC3 in the hepatocytes of high-fat diet (HFD)-fed mice and regulates lipid homeostasis in patients with nonalcoholic fatty liver disease (NAFLD) [126]. This evidence concerns the gene SREBF2 and metabolic dysfunction-associated steatotic liver disease.