Protein / target
NPC1-like intracellular cholesterol transporter 1
Protein at a glance
Biological role
Protein homodimerization activity
Primary system
Endocrine & metabolic
Strongest disease association
Hypercholesterolemia
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
1 approved
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function
Plays a major role in cholesterol homeostasis (PubMed:22095670). Critical for the uptake of cholesterol across the plasma membrane of the intestinal enterocyte (PubMed:22095670). Involved in plant sterol absorption, it transports sitosterol, although at lower rates than cholesterol (By similarity). Is the direct molecular target of ezetimibe, a drug that inhibits cholesterol absorption and is approved for the treatment of hypercholesterolemia (PubMed:15928087). May have a function in the transport of multiple lipids and their homeostasis, thereby influencing lipid metabolism regulation (PubMed:15671032). May be involved in caveolin trafficking from the plasma membrane (By similarity). In addition, acts as a negative regulator of NPC2 and down-regulates its expression and secretion by inhibiting its maturation and accelerating its degradation (PubMed:22095670)
Subcellular location
Domains and Gene Ontology detail (18)Hide
Domains & features
Gene Ontology
- Capical plasma membrane
- Ccytoplasmic vesicle membrane
- Cplasma membrane
- Fcholesterol binding
- Fmyosin V binding
- Fprotein homodimerization activity
- Fsmall GTPase binding
- Fvitamin E binding
- Pcellular response to sterol depletion
- Pcholesterol biosynthetic process
- Pcholesterol homeostasis
- Pcholesterol transport
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
Metabolic enzyme activity
- ·lipoprotein metabolic process
- ·vitamin E metabolic process
Muscle contraction
- ·myosin V binding
View underlying pathways (1)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.
Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.
Drugs targeting this protein
Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.
Niemann-Pick C1-like protein 1 inhibitor
Appears in clinical studies involving hyperlipidemia, Hypercholesterolemia, familial hypercholesterolemia, atherosclerosis
ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.
Translational evidence
Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.
Strongest genetic associations
Human genetic evidence — the most direct causal link between this target and a disease.
Highest-confidence therapeutic associations
Diseases where a drug acting on this target has already reached clinical development.
Highest overall evidence
Remaining associations by Open Targets' aggregated evidence score.
Show all associationsHide all associations
Open Targets ranks 352 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.
Known drugs · 1 total
hyperlipidemia · Hypercholesterolemia · familial hypercholesterolemia
Tractability
Clinical trials
Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.
Show remaining trials (24)Hide
ClinicalTrials.gov via the drug-target graph.
Forefront confidence
Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.
The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.
What's happening now
Recent activity around this target, drawn from one canonical event stream. Every item is reached through a drug that targets this protein, so each event is news about that drug rather than about the protein directly.
- New publicationFixed-dose combination of obicetrapib and ezetimibe for LDL cholesterol reduction (TANDEM): a phase 3, randomised, double-blind, placebo-controlled trial.
- Label change
Label change: EZETIMIBE (ANDA209234)
- Label change
Label change: EZETIMIBE (ANDA209234)
- Label change
Label change: EZETIMIBE (ANDA209234)
- New publicationSmall Interfering RNA to Reduce Lipoprotein(a) in Cardiovascular Disease.
- Convergence high
Ezetimibe lowers LDL cholesterol in hyperlipidaemia — High confidence reached
- Supplemental approval
Supplemental approval: EZETIMIBE (ANDA209234)
- Regulatory approval
Approval: EZETIMIBE (ANDA209234)
- New publicationLow-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel.
- New publicationEzetimibe Added to Statin Therapy after Acute Coronary Syndromes.
- New publicationA randomized, double-blind, placebo-controlled study of the effect of ezetimibe on glucose metabolism in subjects with type 2 diabetes mellitus and hypercholesterolemia.
- New publicationEfficacy and safety of ezetimibe monotherapy in children with heterozygous familial or nonfamilial hypercholesterolemia.
Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.