In addition, the HFD-induced increase in hepatic TG levels (Fig. 6d) and vacuolation in hepatocytes (Fig. 6e) were also normalized with ER stress inhibition in CerS2 heterozygotes, indicating that ER stress is upstream of the SREBP-1 cleavage modulated by CerS2 and plays a critical role in aggravating NAFLD progression in CerS2 heterozygotes. This evidence concerns the gene CERS2 and metabolic dysfunction-associated steatotic liver disease.