Low density lipoprotein (LDL) particles bound to their receptors (LDLR) in coated pits on the cell surface are taken up into clathrin-coated vesicles (Goldstein et al. 1979). In hepatocytes and lymphocytes, but not in fibroblasts, this process requires the presence of an additional protein, LDLRAP1 (ARH1). In human patients, LDLRAP1 deficiency is associated with hypercholesterolemia, emphasizing the central role of the liver in clearance of circulating LDL in vivo (Eden et al. 2002; Garuti et al. 2005; He et al. 2002; Michaely et al. 2004). In vitro, LDLRAP1 protein binds both to LDLR and to components of the clathrin coat, suggesting that it might play an essential bridging function during the movement of LDL:LDLR complexes into clathrin-coated vesicles. This role has not yet been demonstrated in vivo, however, nor is it clear what might substitute for such a bridging function in fibroblasts.