Niemann-Pick C1-like 1 (NPC1L1) is a transmembrane protein that plays a critical role in cholesterol absorption (1). It is highly expressed in small intestine and localized along the brush border in both human and mouse (2,3). NPC1L1 mediates cholesterol uptake via its vesicular endocytosis (4). Ezetimibe, a potent cholesterol absorption inhibitor that is being clinically used to treat hypercholesterolemia (5), prevents NPC1L1 from incorporating into clathrin-coated vesicles and thus inhibits cholesterol uptake (4).