Familial hypercholesterolemia is a automsomal dominant defect, but expressivity is different between homo- and heterozygotes. The biochemical cause of the disease is the defective uptake of low density lipoproteins (LDLs) into cells. These cholesterol-rich lipoproteins accumulate in the blood and can lead to atherosclerosis or other cardiovascular problems. As the peripheral tissues do not receive enough cholesterol, they synthesize additional cholesterol.

The inability to take in LDLs can arise for several reasons: defective LDL receptor that has poor binding affinity to LDL; insufficient or absent LDL receptors on the cell surface; or, inability to endocytose bound LDL receptors.

Hypercholesterolemia is characterized by elevated levels of cholesterol in the blood. This leads to an increased risk of atherosclerosis and other cardiovascular complications. High cholesterol levels can result from excessive cholesterol intake in the diet or from a genetic basis.

Familial hypercholesterolemia is largely affected by the individual's genetics, but the diet also plays an important role in disease progression.