Cholesterol is taken up by enterocytes by a mechanism that requires the Niemann-Pick C1-Like 1 (NPC1L1) transport protein (39, 40). This membrane-associated protein is located at the brush border of enterocytes and is translocated to an intracellular compartment when cells are exposed to cholesterol; current models postulate a clathrin-dependent endocytic mechanism in which NPC1L1 is internalized along with a cholesterol cargo, which then moves through endosomes to the endoplasmic reticulum where it can be packaged into membranes or used to synthesize cholesterol ester (41, 42). NPC1L1 is encoded in the zebrafish genome, and several lines with point mutations in this gene have been created through the Sanger Institute Zebrafish Mutation Project (43). Ezetimibe, an inhibitor of NPC1L1-mediated cholesterol absorption that is used to treat hypercholesterolemia in humans, also blocks dietary cholesterol absorption in larval zebrafish (44–46). This creates an opportunity to use the zebrafish model to study physiological effects of modulating metabolic availability of a single component of a mixed-lipid diet. Regulation of NPC1L1 activity remains largely uncharacterized, although there is evidence from studies in humans given statins (inhibitors of cholesterol synthesis) that NPC1L1 expression levels increase in response to low intracellular cholesterol levels, suggesting that there may be an unidentified genetic mechanism that regulates NPC1L1 expression that could counteract the effects of statins by upregulating import of dietary cholesterol (47).