The study investigates the role of the transcription factor XBP1 in regulating hepatic lipogenesis, which is the process of lipid synthesis in the liver. XBP1, a key regulator of the Unfolded Protein Response (UPR), is induced in the liver by a high carbohydrate diet and directly controls the expression of genes involved in fatty acid synthesis. Deletion of XBP1 in the liver resulted in significant reductions in plasma triglycerides, cholesterol, and free fatty acids without causing hepatic steatosis or significant compromise in protein secretory function. This suggests that XBP1 has an unexpected and critical role in hepatic lipogenesis, distinct from its function in the UPR. The findings have implications for understanding and potentially treating human dyslipidemias.The study investigates the role of the transcription factor XBP1 in regulating hepatic lipogenesis, which is the process of lipid synthesis in the liver. XBP1, a key regulator of the Unfolded Protein Response (UPR), is induced in the liver by a high carbohydrate diet and directly controls the expression of genes involved in fatty acid synthesis. Deletion of XBP1 in the liver resulted in significant reductions in plasma triglycerides, cholesterol, and free fatty acids without causing hepatic steatosis or significant compromise in protein secretory function. This suggests that XBP1 has an unexpected and critical role in hepatic lipogenesis, distinct from its function in the UPR. The findings have implications for understanding and potentially treating human dyslipidemias.