NPC intracellular cholesterol transporter 1 (NPC1)

NPC intracellular cholesterol transporter 1 (NPC1) is an integral membrane protein located predominantly in the late endosomes and lysosomes, where it mediates the export of LDL-derived cholesterol to other cellular compartments. The protein consists of 13 transmembrane helices, a sterol-sensing domain, and three large luminal domains that coordinate cholesterol binding and transfer. NPC1 interacts with NPC2, which initially receives cholesterol from lysosomal digestion and transfers it to NPC1 for transport across the membrane. Disease-causing mutations in NPC1 disrupt this process, leading to accumulation of cholesterol and other lipids in lysosomes—a characteristic feature of Niemann-Pick disease type C. NPC1 also serves as an entry receptor for filoviruses such as Ebola, by binding the viral glycoprotein through its luminal domain. NPC1 function is tightly regulated by the sterol content and inter-domain dynamics, and it is a target for investigational drugs designed to modulate cholesterol trafficking.

Other names

Niemann-Pick C1 proteinNPC1SLC65A1NPC intracellular cholesterol transporter 1Niemann-Pick C1NPC

Direct inhibition of cholesterol transport (by small molecules that bind sterol-sensing domain and block function). Mechanism for Ebola virus entry: binding of viral glycoprotein to NPC1’s domain C enables host cell infection.