Magnesium accumulation upon cyclin M4 silencing activates microsomal triglyceride transfer protein improving NASH

•CNNM4 acts as a magnesium exporter in the liver. Its upregulation in NASH leads to elevated magnesium levels in serum.•Liver-specific CNNM4 targeting alleviates steatosis, inflammation, and fibrosis in preclinical NASH models.•siRNA-mediated CNNM4 downregulation promotes hepatic magnesium accumulation and reduces endoplasmic reticulum stress.•Silencing CNNM4 enhances microsomal triglyceride transfer protein activity leading to VLDL assembly and secretion.