View source for NPC1L1

{{Short description|Mammalian protein found in Homo sapiens}}
{{infobox gene}}
'''Niemann-Pick C1-Like 1''' (NPC1L1) is a [[protein]] found on the [[gastrointestinal tract|gastrointestinal tract's]] [[epithelial]] cells<ref name="Garcia-Calvo2005">{{cite journal | vauthors = Garcia-Calvo M, Lisnock J, Bull HG, Hawes BE, Burnett DA, Braun MP, Crona JH, Davis HR, Dean DC, Detmers PA, Graziano MP, Hughes M, Macintyre DE, Ogawa A, O'neill KA, Iyer SP, Shevell DE, Smith MM, Tang YS, Makarewicz AM, Ujjainwalla F, Altmann SW, Chapman KT, Thornberry NA | display-authors = 6 | title = The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1) | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 102 | issue = 23 | pages = 8132–7 | date = June 2005 | pmid = 15928087 | pmc = 1149415 | doi = 10.1073/pnas.0500269102 | bibcode = 2005PNAS..102.8132G | doi-access = free }}</ref> as well as in [[hepatocytes]].<ref name="Temel">{{cite journal | vauthors = Temel RE, Tang W, Ma Y, Rudel LL, Willingham MC, Ioannou YA, Davies JP, Nilsson LM, Yu L | title = Hepatic Niemann-Pick C1-like 1 regulates biliary cholesterol concentration and is a target of ezetimibe | journal = The Journal of Clinical Investigation | volume = 117 | issue = 7 | pages = 1968–78 | date = July 2007 | pmid = 17571164 | pmc = 1888567 | doi = 10.1172/JCI30060 }}</ref> Specifically, it appears to bind to a critical [[Mediator (coactivator)|mediator]] of [[cholesterol]] absorption.

The drug [[ezetimibe]] inhibits NPC1L1 causing a reduction in cholesterol [[Absorption (small intestine)|absorption]], resulting in a [[blood cholesterol]] reduction of 15-20%.<ref name="pmid17587760">{{cite journal | vauthors = Davis HR, Veltri EP | title = Zetia: inhibition of Niemann-Pick C1 Like 1 (NPC1L1) to reduce intestinal cholesterol absorption and treat hyperlipidemia | journal = Journal of Atherosclerosis and Thrombosis | volume = 14 | issue = 3 | pages = 99–108 | date = June 2007 | pmid = 17587760 | doi = 10.5551/jat.14.99 | doi-access = free }}</ref> [[Gene polymorphism|Polymorphic variations]] in the NPC1L1 [[gene]] could be associated with non-response to ezetimibe treatment.<ref>{{UniProt Full|Q9UHC9|Niemann-Pick C1-like protein 1 precursor - Homo sapiens (Human)}}</ref> One study found that people with [[Inactivating mutation|inactivating mutations]] in the NPC1L1 gene had a lower [[Low-density lipoprotein#Testing|LDL cholesterol level]], as well as an around 50% reduction in the risk of [[Coronary artery disease|coronary heart disease]].<ref>{{Cite journal |last=Myocardial Infarction Genetics Consortium Investigators |last2=Stitziel |first2=Nathan O. |last3=Won |first3=Hong-Hee |last4=Morrison |first4=Alanna C. |last5=Peloso |first5=Gina M. |last6=Do |first6=Ron |last7=Lange |first7=Leslie A. |last8=Fontanillas |first8=Pierre |last9=Gupta |first9=Namrata |last10=Duga |first10=Stefano |last11=Goel |first11=Anuj |last12=Farrall |first12=Martin |last13=Saleheen |first13=Danish |last14=Ferrario |first14=Paola |last15=König |first15=Inke |date=2014-11-27 |title=Inactivating mutations in NPC1L1 and protection from coronary heart disease |url=https://pubmed.ncbi.nlm.nih.gov/25390462/ |journal=The New England Journal of Medicine |volume=371 |issue=22 |pages=2072–2082 |doi=10.1056/NEJMoa1405386 |issn=1533-4406 |pmc=4335708 |pmid=25390462}}</ref>

NPC1L1 has been shown to be an [[accessory receptor]] for [[hepatitis C virus]] entry into cells, and thus ezetimibe might be used as a therapeutic strategy.<ref>{{cite journal | vauthors = Sainz B, Barretto N, Martin DN, Hiraga N, Imamura M, Hussain S, Marsh KA, Yu X, Chayama K, Alrefai WA, Uprichard SL | title = Identification of the Niemann-Pick C1-like 1 cholesterol absorption receptor as a new hepatitis C virus entry factor | journal = Nature Medicine | volume = 18 | issue = 2 | pages = 281–5 | date = January 2012 | pmid = 22231557 | pmc = 3530957 | doi = 10.1038/nm.2581 }}</ref>

As [[cancer]] appeared more frequently in patients treated with [[simvastatin]]-[[ezetimibe]] combination therapy in one clinical trial,<ref name="pmid18765433">{{cite journal | vauthors = Rossebø AB, Pedersen TR, Boman K, Brudi P, Chambers JB, Egstrup K, Gerdts E, Gohlke-Bärwolf C, Holme I, Kesäniemi YA, Malbecq W, Nienaber CA, Ray S, Skjaerpe T, Wachtell K, Willenheimer R | display-authors = 6 | collaboration = SEAS Investigators | title = Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis | journal = The New England Journal of Medicine | volume = 359 | issue = 13 | pages = 1343–56 | date = September 2008 | pmid = 18765433 | doi = 10.1056/NEJMoa0804602 | doi-access = free }}</ref> it had been [[hypothesized]] that NPC1L1 inhibition by ezetimibe might be associated with an increased cancer risk.<ref name="pmid18765432">{{cite journal | vauthors = Peto R, Emberson J, Landray M, Baigent C, Collins R, Clare R, Califf R | title = Analyses of cancer data from three ezetimibe trials | journal = The New England Journal of Medicine | volume = 359 | issue = 13 | pages = 1357–66 | date = September 2008 | pmid = 18765432 | doi = 10.1056/NEJMsa0806603 | doi-access = free }}</ref> However, a [[meta-analysis]] of ezetimibe [[Clinical trial|clinical data]] showed no increase in the risk of cancer from treatment with ezetimibe.<ref name="pmid26301648">{{cite journal | vauthors = Savarese G, De Ferrari GM, Rosano GM, Perrone-Filardi P | title = Safety and efficacy of ezetimibe: A meta-analysis | journal = International Journal of Cardiology | volume = 201 | pages = 247–52 | date = December 2015 | pmid = 26301648 | doi = 10.1016/j.ijcard.2015.08.103 }}</ref>

== References ==
{{Reflist}}

== External links ==
{{commons category}}
* {{MeshName|NPC1L1+protein,+human}}
* {{PDBe-KB2|Q9UHC9|Human NPC1-like intracellular cholesterol transporter 1}}