Brown and Goldstein described the classical pathway of low-density lipoprotein (LDL) catabolism in human fibroblasts, initiated by LDL-binding to the LDL receptor (LDLR) and followed by endocytosis and lysosomal catabolism of its components. 1 The initial steps in the hepatic catabolism of chylomicron remnants and large very-low-density lipoprotein (VLDL) remnants have turned out to be more complex, involving initial binding to other cell surface molecules, including heparan sulfate proteoglycans (HSPGs), apo E, and hepatic lipase (HL), followed by transfer to endocytic receptors (LDLR and LDLR-related protein [LRP]). 2 Apo E was first demonstrated on hepatocyte surfaces in rat liver. 3 At the light microscopic level, the bulk of hepatic apo E was in the space of Disse. At the electron microscopic level, this apo E was found exclusively on microvilli, occasionally associated with an evident lipoprotein particle. Virtually no apo E was in the electron-lucent matrix. HL is also associated mainly with basolateral microvilli of hepatocytes in rat liver4 and in rabbit liver transfected with human HL. 5 Apo E-deficient mice are dysbetalipoproteinemic, with massive accumulation of remnants in the blood. 6 In mice doubly deficient in apo E and HL, accumulation of lipoproteins in the blood is even greater and includes vesicular lipoproteins, suggesting further impairment of endocytosis, together with selective uptake of cholesteryl esters, presumably by scavenger receptor B1. 7