The Ca2+ stored in the cellular endoplasmic reticulum (ER) plays a crucial role in protein folding and lipid transfer, and its impairment leads to cellular ER stress. When chronic cellular ER stress occurs in the liver, it triggers the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). Previous reports found that NACHT and WD repeat domain containing 1 (NWD1) localized in the ER and mitochondria in neural stem/progenitor cells, but the significance of NWD1 outside the brain is not well known.