Niemann-Pick C1-like protein 1 (NPC1L1) (NPC1L1)

Niemann-Pick C1-like protein 1 (NPC1L1) is a multi-pass transmembrane protein primarily expressed on the apical membrane of enterocytes in the small intestine and the canalicular membrane of hepatocytes in the liver [1, 3, 12]. Its primary biological function is to facilitate the absorption of dietary and biliary cholesterol from intestinal micelles into the bloodstream [1, 5]. NPC1L1 operates through a clathrin-mediated endocytic pathway, internalizing cholesterol molecules to maintain sterol homeostasis [2, 12, 18]. In the liver, it plays a crucial role in the re-uptake of cholesterol from bile, thereby preventing excessive biliary cholesterol loss [5, 16]. NPC1L1 is a major therapeutic target for the treatment of hypercholesterolemia and the prevention of cardiovascular diseases [2, 6, 15]. The drug ezetimibe specifically binds to the extracellular loop of NPC1L1, inhibiting its ability to transport cholesterol and resulting in a significant reduction in plasma low-density lipoprotein (LDL) cholesterol levels [1, 2, 14]. Beyond its role in lipid metabolism, NPC1L1 has been implicated in the entry of the hepatitis C virus into host cells and the development of gallstones [3, 12, 16]. Genetic variants of NPC1L1 are associated with varying efficiencies in sterol absorption and individual responses to cholesterol-lowering therapies [1, 13].

Other names

NPC1-like intracellular cholesterol transporter 1SLC65A2LDLCQ7NPC1L1

Inhibition of NPC1L1-mediated cholesterol uptake from intestinal micelles and biliary re-uptake in the liver