The low density lipoprotein receptor (LDLR protein) gene family consists of cell surface proteins involved in receptor-mediated endocytosis of specific ligands. Low density lipoprotein (LDL) is normally bound at the cell membrane and taken into the cell ending up in lysosomes where the protein is degraded and the cholesterol is made available for repression of microsomal enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, the rate-limiting step in cholesterol synthesis. At the same time, a reciprocal stimulation of cholesterol ester synthesis takes place. Mutations in this gene cause the autosomal dominant disorder, familial hypercholesterolemia. In case of HIV-1 infection, it functions as a receptor for extracellular Tat in neurons, mediating its internalization in uninfected cells. PCSK9 binds to the epidermal growth factor-like repeat A (EGF-A) domain of the LDLR protein, inducing LDLR degradation.