Familial hypercholesterolemia is a genetic disorder in which cholesterol levels in the blood are very high. There are several genes which can affect cholesterol levels. The type we will study is an autosomal recessive genetic disorder. This means that only people with two recessive alleles of this gene are unable to transport cholesterol to the liver cells that metabolize it. Cholesterol is carried through the bloodstream in a low-density lipoprotein (LDL, a protein and lipid containing particle). In normal people, the lipoprotein binds to a specific receptor on the liver cell surface and is then taken up into the cell by endocytosis.

Some people who have the disorder lack a fully functional lipoprotein, named Apolipoprotein E, due to a point mutation in the genetic sequence that encodes the protein. In the point mutant, an arginine amino acid in position 158 is mutated into a cysteine amino acid. This changes the conformation of the protein and the cholesterol-carrying lipoprotein cannot enter the cell because it cannot successfully attach itself to the receptor protein on the liver cell. The excess cholesterol can build up on the inner walls of the blood vessels, which can lead to blockage in the arteries, causing a heart attack, or a blood clot in the brain, leading to a stroke. there are also other genetic problems that cause this disease, such as mutations in the lipoprotein receptor, but in this tutorial we will deal only with Apolipoprotein E.