Niemann-Pick C1-Like 1: A Key Player in Intestinal Cholesterol Absorption

概要

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Niemann-Pick C1-Like 1 (NPC1-L1), as its name indicates, was identified in 2000 as a homolog of NPC1. Its major physiological function was clarified by a research group in Shöring’s laboratory who had long been searching for a target of ezetimibe, a cholesterol-lowering drug. They published a paper on 2004 in Science, reporting a reduction of intestinal cholesterol absorption and a lack of effects of ezetimibe in NPC1-L1 knockout mice. With subsequent studies that confirmed their findings, it is now clear that NPC1-L1 is a key player in one of the major pathways of intestinal cholesterol absorption and that it is the target of ezetimibe. This review summarizes what has been shown up to now about the structure and function of NPC1-L1. This review also refers to ABCG5/G8, a member of ABC family transporters, which co-localizes with NPC1-L1 on the intestinal epithelial cells and appears to work in a closely related manner.