Hepatic HSPGs exhibit extreme structural features of their carbohydrate side-chains that enhance ligand binding. Thus, HSPGs in the liver rapidly pull apoB₄₈ remnant lipoproteins out of plasma via interactions with positively charged proteins on the particles, chiefly LpL and apoE. Once in the liver, the particles encounter hepatic lipase (HL), which serves as an additional bridging molecule between HSPGs and lipoproteins. Shown are 2 pathways for particle clearance. The first is direct receptor-mediated uptake, in which cholesteryl ester–rich apoB₄₈ remnant lipoproteins pass from the hepatic sinusoid through the fenestrated endothelium and then bind directly to integral plasma membrane receptors (red arrows; shown are the LDL receptor, which binds apoE, and the syndecan and glypican HSPGs, which bind LpL, hepatic lipase, and apoE). The second clearance mechanism is a cooperative pathway, in which apoB₄₈ remnant lipoproteins from the hepatic sinusoid are first sequestered by matrix HSPGs within the space of Disse and then taken up in cooperation with the integral plasma membrane receptors (blue arrows; shown are the collagen XVIII and perlecan HSPGs). Also shown is one of several secreted enzymes (Enz), such as heparanase or the heparan 6-O-endosulfatases, that are expressed by liver, degrade HSPGs, and may dampen these processes.