Niemann–Pick C1-like 1 protein (NPC1L1)

Niemann–Pick C1-like 1 protein (NPC1L1) is a multi-pass transmembrane sterol transporter primarily expressed on the apical membrane of enterocytes in the small intestine and on hepatocytes in the liver. It is critically responsible for the intestinal absorption of dietary and biliary cholesterol. NPC1L1 contains a sterol-sensing domain and cycles between the cell membrane and intracellular compartments depending on cholesterol availability. It acts via clathrin-mediated endocytosis to internalize cholesterol, regulating cholesterol homeostasis in the body. Its function makes it a key molecular target for the cholesterol absorption inhibitor ezetimibe, which lowers LDL cholesterol and cardiovascular risk. Genetic variations in NPC1L1 may affect drug efficacy and individual susceptibility to hypercholesterolemia or cardiovascular disease. NPC1L1 also serves as a cofactor for hepatitis C virus entry into hepatocytes and may play secondary roles in lipid-related liver disorders.

Other names

NPC1L1Niemann-Pick C1-Like 1 transporterNiemann-Pick C1-Like intracellular cholesterol transporter 1

Inhibition of intestinal cholesterol absorption by blocking transporter-mediated uptake (e.g., Ezetimibe binds and inhibits NPC1L1 at the brush border of enterocytes, reducing plasma LDL cholesterol). Modulation of hepatobiliary cholesterol excretion.