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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:2433.)
© 2006 American Heart Association, Inc.

Brief Reviews

NPC1L1: Evolution From Pharmacological Target to Physiological Sterol Transporter

Murray W. Huff; Rebecca L. Pollex; Robert A. Hegele

From Vascular Biology Group, Robarts Research Institute, London, Ontario, Canada.

Correspondence to Robert A. Hegele, Blackburn Cardiovascular Genetics Laboratory, Robarts Research Institute, 100 Perth Drive, Room 406, London, Ontario, Canada, N6A 5K8. E-mail hegele{at}robarts.ca

Niemann-Pick C1-like 1 protein (NPC1L1) was recently shown to be the molecular target of the cholesterol absorption inhibitor class of drugs, of which ezetimibe is the first widely used member. Since its discovery, NPC1L1 has also been shown to play a focal physiological role in intestinal absorption of sterols, including plant sterols and cholesterol. Evidence in support of this new metabolic pathway has been garnered not only through human, animal, and cell studies of function but also through the use of human genetics as an approach to study the association of NPC1L1 sequence variation with metabolic and drug-response phenotypes. The example of NPC1L1 shows how the elucidation of a pharmacological target can serve as a means to gain understanding of a key physiological pathway.

Niemann-Pick C1-like 1 protein (NPC1L1) was recently shown to be the molecular target of the cholesterol absorption inhibitor, ezetimibe. Evidence in support of a focal physiological role for NPC1L1 in intestinal sterol absorption has been garnered not only through human, animal, and cell studies but also through the use of human genetics.

Key Words: cholesterol • enterocyte • intestine • lipoproteins • low-density lipoprotein • pharmacogenetics • sterol

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