Apolipoprotein E (apo E) is one of the apolipoprotein components in very low density lipoproteins (VLDL) and high density lipoproteins (HDL). Apo E binds to low density lipoprotein (LDL) receptors and apo E-specific remnant receptors, and regulates remnant lipoprotein metabolism through these receptors in the liver. In the general population, apo E shows genetic heterogeneity, with three alleles (epsilon 4, epsilon 3, and epsilon 4) which produce apo E isoproteins, apo E4, apo E3, and apo E2, respectively. Apo E2 is defective in its binding to lipoprotein receptors, resulting in the accumulation of lipoprotein remnants in the plasma. Type III hyperlipoproteinemia appears in a few percent of the individuals who are homozygous for apo E2 and the development of hyperlipoproteinemia requires the presence of other genetic or environmental factors. Even heterozygous individuals with apo E2 or apo E4 differ from those with only apo E3 in plasma lipoprotein metabolism. Subjects with an E3/2 phenotype had reduced LDL and increased VLDL levels, and those with an E4/3 phenotype had increased LDL levels in serum. In addition to these common apo E isoproteins, there are several unique mutants of apo E, which are associated with hyperlipoproteinemia and atherosclerosis.