NPC1L1

Class

Cholesterol-absorption inhibitor

NPC1L1 (Niemann-Pick C1-Like 1) is a transporter protein located on the surface of intestinal cells lining the small bowel, and to a lesser extent in liver cells. Its normal role is to bind dietary and biliary cholesterol in the gut lumen and shuttle it into the cell, the first step in absorbing cholesterol into the bloodstream. Blocking this transporter reduces the amount of cholesterol taken up from the intestine, which in turn lowers the supply of cholesterol delivered to the liver. The liver responds by increasing uptake of low-density lipoprotein (LDL) particles from the blood to compensate, which lowers circulating LDL cholesterol, a lipid strongly associated with atherosclerotic cardiovascular disease. This mechanism is distinct from cholesterol-synthesis inhibition, so it offers a complementary route to lowering LDL cholesterol, particularly relevant for cardiovascular risk reduction, lipid disorders, and management of elevated cholesterol that persists despite other interventions. Because absorption inhibition works locally in the gut rather than throughout the body, it is generally considered a targeted approach to modifying one specific input into overall cholesterol balance.