PNPLA3 and metabolic dysfunction-associated steatohepatitis: ER stress plays a crucial role in NASH progression.24 Lipid droplets (LDs) originate from the ER and regulate ER stress.25 In both HuH7 cells26 and I148M mutation knock‐in mice,16 PNPLA3 I148M mutant protein, but not wild‐type PNPLA3, was found to localize mainly in LDs.