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

Niemann-Pick C1-like 1 (NPC1L1) is a multi-pass transmembrane protein that serves as the primary mediator of cholesterol and phytosterol absorption in the small intestine [1][4]. Located on the apical membrane of enterocytes, NPC1L1 facilitates the uptake of dietary and biliary cholesterol from the intestinal lumen into the cell via a clathrin-mediated endocytic pathway [1][3]. In humans, NPC1L1 is also expressed on the canalicular membrane of hepatocytes, where it promotes the reabsorption of cholesterol from bile back into the liver, further regulating systemic cholesterol levels [1][2]. Dysregulation or high activity of this protein is directly linked to hypercholesterolemia and an increased risk of atherosclerotic cardiovascular disease [3][4]. The protein is the specific molecular target of ezetimibe, a lipid-lowering medication that binds to the extracellular loop of NPC1L1 to block cholesterol transport [2][5]. By inhibiting this pathway, NPC1L1 antagonists effectively reduce the delivery of intestinal cholesterol to the liver, leading to an up-regulation of hepatic LDL receptors and a subsequent decrease in circulating low-density lipoprotein cholesterol (LDL-C) [2][3].

Other names

NPC1L1Niemann-Pick C1-like protein 1

Inhibition of NPC1L1-mediated cholesterol uptake in the small intestine and reabsorption in the liver.