SLC25A47 is a liver-specific mitochondrial NAD+ transporter that functions as a metabolic regulator of hepatic energy homeostasis and lipid metabolism 1. The protein transports NAD+ across the mitochondrial membrane to support SIRT3 deacetylase activity, which activates AMPK signaling to suppress lipogenesis and cholesterol synthesis 1. SLC25A47 also regulates hepatic gluconeogenesis by controlling pyruvate flux and malate accumulation in mitochondria 2. Metformin transcriptionally activates SLC25A47 expression as part of its metabolic effects 1. In disease contexts, SLC25A47 deficiency increases hepatic lipid accumulation, triglycerides, and cholesterol levels in mice 1. Hepatic SLC25A47 downregulation is associated with enhanced hepatocellular carcinoma development through mTOR pathway activation 1. Conversely, mesenchymal stem cell transplantation improves liver fibrosis by upregulating SLC25A47 expression, enhancing mitochondrial NAD+ levels and SIRT3 activity to restore mitochondrial function 3. Human genetic studies link SLC25A47 variants to fasting glucose, HbA1c, and cholesterol levels 2. However, one study reported minimal impacts of SLC25A47 on hepatic lipid metabolism during fasting and high-fat feeding 4, suggesting context-dependent physiological roles. The precise transport mechanism remains incompletely characterized 1.