Role of SR-BI in HDL metabolism in vivo. HDL is thought to extract cellular cholesterol from peripheral tissues by a mechanism involving the product of the ABCA1 (Tangier disease) gene. After the plasma HDL-cholesterol (HDL-C) is esterified to cholesteryl ester (CE) by the enzyme lipoprotein lipase (not shown), it can be transported to the liver by either an indirect pathway (transfer to other lipoproteins followed by hepatic receptor-mediated endocytosis, not shown) or a direct pathway via SR-BI and selective cholesterol uptake. The HDL-C in the liver can be secreted into the bile, either as cholesterol or as bile acids. The delivery of cholesterol from peripheral tissues via plasma HDL to the liver for biliary excretion as cholesterol or bile acids is called “reverse cholesterol transport.” SR-BI also can mediate HDL-C uptake by steroidogenic tissues for steroid hormone synthesis or cholesterol storage. Redrawn from refs. 11, 34.