LDL receptor mediates the endocytosis of cholesterol-rich LDL and thus maintains the plasma level of LDL. This occurs in all nucleated cells, but mainly in the liver which removes ~70% of LDL from the circulation. LDL receptors are clustered in clathrin-coated pits, and coated pits pinch off from the surface to form coated endocytic vesicles that carry LDL into the cell. After internalization, the receptors dissociate from their ligands when they are exposed to lower pH in endosomes. After dissociation, the receptor folds back on itself to obtain a closed conformation and recycles to the cell surface. The rapid recycling of LDL receptors provides an efficient mechanism for delivery of cholesterol to cells. It was also reported that by association with lipoprotein in the blood, viruses such as hepatitis C virus, Flaviviridae viruses and bovine viral diarrheal virus could enter cells indirectly via LDLR-mediated endocytosis. LDLR has been identified as the primary mode of entry for the Vesicular stomatitis virus in mice and humans. In addition, LDLR modulation is associated with early atherosclerosis-related lymphatic dysfunction. Synthesis of receptors in the cell is regulated by the level of free intracellular cholesterol; if it is in excess for the needs of the cell then the transcription of the receptor gene will be inhibited. LDL receptors are translated by ribosomes on the endoplasmic reticulum and are modified by the Golgi apparatus before travelling in vesicles to the cell surface.