Here, we have extended our characterization of XBP1 as a molecular component of the 12-h clock4, showing that XBP1 plays a key role in controlling membrane fluidity and its ability to properly maintain phospholipid composition and lipid homeostasis, linking the 12-h clock to the onset and progression of a type of NAFLD development via XBP1s transcriptional regulation. The gene discussed is CLOCK; the disease is metabolic dysfunction-associated steatotic liver disease.