How Goldstein and Brown Found the LDL Receptor and Receptor-Mediated Endocytosis

Michael Brown and Joseph Goldstein traced familial hypercholesterolemia, an autosomal dominant disorder in which LDL accumulates in skin, blood and artery walls and causes heart disease in the young, to a missing feedback response in cells. Around 1973 they found patients' LDL was normal but cells could not sense it to shut down their own cholesterol synthesis, pointing to a membrane receptor. They identified the LDL receptor, showed FH stems from inactivating mutations in it, and established receptor-mediated endocytosis, work honoured with the 1985 Nobel Prize.