Gene and Protein Information
Species	TM	AA	Chromosomal Location	Gene Symbol	Gene Name	Reference
Human	13	1359	7p13	NPC1L1	NPC1 like intracellular cholesterol transporter 1
Mouse	13	1333	11 A1	Npc1l1	NPC1 like intracellular cholesterol transporter 1
Rat	13	1331	14q21	Npc1l1	NPC1 like intracellular cholesterol transporter 1

Previous and Unofficial Names

Niemann-Pick C1-like protein 1 | NPC1-like 1 | NPC1 like 1

Database Links
Specialist databases
RESOLUTE	NPC1L1 (Hs)
Other databases
Alphafold	Q9UHC9 (Hs), Q6T3U4 (Mm), Q6T3U3 (Rn)
ChEMBL Target	CHEMBL2027 (Hs), CHEMBL1075296 (Mm), CHEMBL5161 (Rn)
DrugBank Target	Q9UHC9 (Hs)
Ensembl Gene	ENSG00000015520 (Hs), ENSMUSG00000020447 (Mm), ENSRNOG00000049955 (Rn)
Entrez Gene	29881 (Hs), 237636 (Mm), 432367 (Rn)
Human Protein Atlas	ENSG00000015520 (Hs)
KEGG Gene	hsa:29881 (Hs), mmu:237636 (Mm), rno:432367 (Rn)
OMIM	608010 (Hs)
Pharos	Q9UHC9 (Hs)
RefSeq Nucleotide	NM_013389 (Hs), NM_207242 (Mm), NM_001002025 (Rn)
RefSeq Protein	NP_037521 (Hs), NP_997125 (Mm), NP_001002025 (Rn)
UniProtKB	Q9UHC9 (Hs), Q6T3U4 (Mm), Q6T3U3 (Rn)
Wikipedia	NPC1L1 (Hs)

Selected 3D Structures
	Description:  The structure of the NPC1L1 N-terminal domain in a closed conformation. PDB Id:  3QNT Resolution:  2.83Å Species:  Human References:  5
	Description:  Cryo-EM structure of NPC1L1 in apo form. PDB Id:  6V3F Resolution:  3.7Å Species:  Rat References:  4
	Description:  Structure of NPC1-like intracellular cholesterol transporter 1 (NPC1L1) in complex with an ezetimibe analog PDB Id:  6V3H Resolution:  3.5Å Species:  Rat References:  4

Substrates and Reaction Kinetics
Substrate Sp. Property Value Units Standard property Standard value Assay description Assay conditions Comments Reference Cholesterol N/A - - 1

Download all structure-activity data for this target as a CSV file

Antagonists
Key to terms and symbols	View all chemical structures	Click column headers to sort
Ligand Sp. Action Value Parameter Reference ezetimibe Hs Inhibition 6.7 pKd 2 ⤷ pKd 6.7 (Kd 2.2x10-7 M) [2] Description: Measure of ezetimibe glucuronide binding to NPC1L1

Functional Assays
In vitro 3H-cholesterol uptake assay. Species:  Human Tissue:  Madin-Darby Canine Kidney II (MDCKII) cells stably expressing human NPC1L1 Response measured:  Increase in intracellular 3H-cholesterol. References:  3

Clinically-Relevant Mutations and Pathophysiology Comments

Two rare polymorphisms in the NPC1L1 gene are associated with a non-reponse to ezetimibe in hyperlipidemia patients. For more details see the OMIM entry linked to from this target page.

General Comments
NPC1L1 acts in the gut epithelium to allow the accumulation of dietary cholesterol through a clathrin-dependent mechanism. Ezetimibe is used to reduce cholesterol absorption through inhibition of NPC1L1. Analysis of cryo-EM structures reveals how NPC1L1 transports cholesterol and the mechanism of ezetimibe inhibition [3].