STARD5 (StAR related lipid transfer domain containing 5) is a cytosolic lipid transport protein that plays a crucial role in cellular cholesterol homeostasis and bile acid metabolism. The protein contains a START domain and functions primarily as a bile acid-binding protein rather than a cholesterol transporter, with specific affinity for primary bile acids such as cholic acid and chenodeoxycholic acid, and higher affinity for secondary bile acids like deoxycholic acid 1 2. Unlike other START domain proteins, STARD5 does not bind cholesterol directly but can bind the regulatory oxysterol 25-hydroxycholesterol 3. STARD5 is predominantly expressed in liver and kidney tissues and is regulated by endoplasmic reticulum stress rather than sterol levels, distinguishing it from related family members like STARD4 4 5. The protein regulates plasma membrane cholesterol content and intracellular cholesterol homeostasis, with its ablation leading to decreased plasma membrane cholesterol, reduced cholesterol efflux, and increased neutral lipid accumulation 6. Clinically, STARD5 deficiency accelerates hepatic steatosis and fibrosis progression through dysregulation of oxysterol signaling pathways 7, while reduced STARD5 expression in hepatocellular carcinoma correlates with poor prognosis 8.