LDLR

About LDLR

LDLR on chromosome 19p13.2 encodes the low density lipoprotein receptor, which removes LDL cholesterol from the blood, mainly in the liver, by receptor mediated endocytosis. After releasing its cargo in endosomes, the receptor recycles back to the cell surface. Michael Brown and Joseph Goldstein discovered the receptor and this pathway through studies of familial hypercholesterolemia, work recognized by the 1985 Nobel Prize in Physiology or Medicine. Pathogenic LDLR variants are the most common cause of familial hypercholesterolemia, an autosomal dominant disorder that affects roughly 1 in 250 people in its heterozygous form. It causes markedly elevated LDL cholesterol from birth, premature coronary artery disease, tendon xanthomas especially of the Achilles tendon, xanthelasma, and corneal arcus. The much rarer homozygous form causes extremely high cholesterol and coronary disease in childhood or adolescence. Variants in APOB and PCSK9 cause clinically similar disease. Statins, ezetimibe, and PCSK9 inhibitors such as evolocumab and alirocumab are used to lower LDL. Familial hypercholesterolemia is thought to be substantially underdiagnosed worldwide, and cascade testing of relatives is used to identify additional affected family members.