ArticleScience advances2020
Cryo-EM structures of NPC1L1 reveal mechanisms of cholesterol transport and ezetimibe inhibition.
Article in Science advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- The promising novel therapies for familial hypercholesterolemia.Journal of clinical laboratory analysis · 2022Pooled it
- Dual functions of NPC1L1 for cholesterol transport: Cholesterol capture and regulation of inner-leaflet cholesterol accessibility.iScience · 2026Article
- Chitosan-TPP modification of SNEDDS enhances mucin interaction, apparent epithelial transport, and oral exposure of ezetimibe.Drug delivery and translational research · 2026Article
- Hypocholesterolemic agents and the gut microbiota: a review of interactions and modulatory activity.Pharmacological reports : PR · 2026Review
- Niemann-Pick C1-Like 1 in Cholesterol Absorption and Homeostasis: Mechanisms, Regulation, and Emerging Phytochemical Inhibitors.Current issues in molecular biology · 2026Review
- Competition between a transmembrane helix on Scap and a membrane cholesterol regulates Scap-Insig interaction and SREBP activation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Ergosterol as a natural modulator of intestinal cholesterol absorption via NPC1L1: anFrontiers in bioinformatics · 2026Article
- Cholesterol metabolism: molecular mechanisms, biological functions, diseases, and therapeutic targets.Molecular biomedicine · 2025Review
- The Role of Cholesterol Metabolism and Its Regulation in Tumor Development.Cancer medicine · 2025Review
- Identification of a Novel NPC1L1 Inhibitor from Danshen and Its Role in Nonalcoholic Fatty Liver Disease.International journal of molecular sciences · 2025Article
- Nonvesicular cholesterol transport in physiology.The Journal of clinical investigation · 2025Review
- Albumin-Based Nanoparticles with Factorial Design as a Promising Approach for Remodeled Repaglinide: Evidence from In Silico, In Vitro, and In Vivo Evaluations.Pharmaceutics · 2025Article
- NPC1L1 on pancreatic adenocarcinoma cell functions as a two-pronged checkpoint against antitumor activity.Innovation (Cambridge (Mass.)) · 2025Article
- Mechanism and therapeutic potential of liver injury induced by cholesterol-associated proteins.Frontiers in pharmacology · 2025Review
- Potential function of hepatic Niemann-Pick C1-like 1: cholesterol homeostasis regulation of the canalicular lipid bilayer membrane.Gastroenterology report · 2025Review
- Potential lipid-lowering effects of preussin B on inhibition of intestinal cholesterol absorption: integrative mechanisms of action and proteomic analysis.Frontiers in pharmacology · 2025Article
- In silico comparative analysis of cestode and human NPC1 provides insights for ezetimibe repurposing to visceral cestodiases treatment.Scientific reports · 2024Article
- Why make it if you can take it: review on extracellular cholesterol uptake and its importance in breast and ovarian cancers.Journal of experimental & clinical cancer research : CR · 2024Review
- Structure and dynamics of cholesterol-mediated aquaporin-0 arrays and implications for lipid rafts.eLife · 2024Article
- Repositioning of ezetimibe for the treatment of idiopathic pulmonary fibrosis.The European respiratory journal · 2024Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
The intestinal absorption of cholesterol is mediated by a multipass membrane protein, Niemann-Pick C1-Like 1 (NPC1L1), the molecular target of a cholesterol lowering therapy ezetimibe. While ezetimibe gained Food and Drug Administration approval in 2002, its mechanism of action has remained unclear. Here, we present two cryo-electron microscopy structures of NPC1L1, one in its apo form and the other complexed with ezetimibe. The apo form represents an open state in which the N-terminal domain (NTD) interacts loosely with the rest of NPC1L1, leaving the NTD central cavity accessible for cholesterol loading. The ezetimibe-bound form signifies a closed state in which the NTD rotates ~60°, creating a continuous tunnel enabling cholesterol movement into the plasma membrane. Ezetimibe blocks cholesterol transport by occluding the tunnel instead of competing with cholesterol binding. These findings provide insight into the molecular mechanisms of NPC1L1-mediated cholesterol transport and ezetimibe inhibition, paving the way for more effective therapeutic development.
Identifiers
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.