Potential function of hepatic Niemann-Pick C1-like 1: cholesterol homeostasis regulation of the canalicular lipid bilayer membrane

Niemann-Pick C1-like 1 (NPC1L1) is distributed in the human liver and intestine but only slightly expressed in the mouse liver. While it is well established that intestinal NPC1L1 is crucial for the absorption of exogenous cholesterol, the physiological and pathological roles of canalicular membrane-localized NPC1L1 in human hepatic cholesterol transport remain unclear. In this review, we discussed the potential function of human hepatic NPC1L1 and proposed that the disparity in NPC1L1 abundance between humans and mice in the liver may be attributable to their distinct bile hydrophobicity. Human hepatic NPC1L1 might interact with other proteins in the canalicular membrane, regulate membrane cholesterol homeostasis, and contribute to the stability of the canalicular lipid bilayer membrane in response to the greater detergent properties of human bile salts. We hoped to provide novel perspectives on hepatic NPC1L1 for future investigations.