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

Niemann-Pick C1-like 1 (NPC1L1) transporter protein is a multi-spanning membrane protein primarily located in the brush border of small intestinal epithelial cells and hepatocytes, where it functions as a sterol transporter critical for intestinal cholesterol absorption and the maintenance of cholesterol homeostasis[5][6]. NPC1L1 facilitates the uptake of dietary and biliary cholesterol through a mechanism involving dynamic conformational changes in its N-terminal domain, which binds cholesterol and transports it across the cell membrane via endocytic vesicular trafficking[1][3][6]. The protein is the canonical target of the lipid-lowering drug ezetimibe, which inhibits cholesterol absorption by blocking the transporter’s function[1][3][7]. NPC1L1 is structurally related to Niemann-Pick C1 (NPC1) and is characterized by multiple transmembrane domains and domain flexibility essential to its function[5][7]. Beyond cholesterol regulation, emerging research implicates NPC1L1 in cancer biology, highlighting its broader significance[5]. Inhibition or genetic variation of NPC1L1 impacts risk and progression of cardiovascular disease by modulating cholesterol uptake, with clinical biomarker applications focusing on NPC1L1 expression for guiding therapy and risk assessment.

Other names

Niemann-Pick C1-Like 1NPC1L1 protein

Inhibition of cholesterol uptake: Ezetimibe and its analogs bind to NPC1L1, blocking the cholesterol transport pathway and preventing absorption in enterocytes[1][3][7].