NPC1L1

Niemann-Pick C1-Like 1 (NPC1L1) is a protein found on the gastrointestinal tract's epithelial cells as well as in hepatocytes. Specifically, it appears to bind to a critical mediator of cholesterol absorption.

The drug ezetimibe inhibits NPC1L1 causing a reduction in cholesterol absorption, resulting in a blood cholesterol reduction of 15-20%. Polymorphic variations in the NPC1L1 gene could be associated with non-response to ezetimibe treatment. One study found that people with inactivating mutations in the NPC1L1 gene had a lower LDL cholesterol level, as well as an around 50% reduction in the risk of coronary heart disease.

NPC1L1 has been shown to be an accessory receptor for hepatitis C virus entry into cells, and thus ezetimibe might be used as a therapeutic strategy.

As cancer appeared more frequently in patients treated with simvastatin-ezetimibe combination therapy in one clinical trial, it had been hypothesized that NPC1L1 by ezetimibe might be associated with an increased cancer risk. However, a meta-analysis of ezetimibe clinical data showed no increase in the risk of cancer from treatment with ezetimibe.