The focus of the LDL receptor (LDLR) project is to characterize the mechanisms by which the LDLR mediates lipoprotein-uptake. The LDLR is responsible for the clearance of very low density lipoprotein (VLDL), VLDL remnants and low density lipoprotein (LDL) from the circulation. All three lipoproteins are atherogenic and defects in the LDLR result in elevated levels of these lipoproteins, particularly LDL. Loss-of-function mutations in the LDLR result in elevated levels of these atherogenic lipoproteins, resulting in accelerated atherosclerosis and increased risk of coronary artery disease. Ongoing work by our group has shown that the LDLR uses different mechanisms to support uptake of LDL and VLDL/VLDL remnants. In part, these different mechanisms are mediated by selective use of different cytosolic adaptor proteins to couple the LDLR to endocytic machinery. The molecular details of these uptake mechanisms are under investigation.