Protein / target
NPC1-like intracellular cholesterol transporter 1
Protein at a glance
Biological role
Protein homodimerization
Strongest disease association
Metabolic Diseases
Therapeutic position
Established drug target
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function overview
Plays a major role in cholesterol homeostasis.
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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.
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Lipid & lipoprotein metabolism
- ·Plays a major role in cholesterol homeostasis (PubMed:22095670). Critical for the uptake…
- ·cholesterol binding
- ·cellular response to sterol depletion
- ·cholesterol biosynthetic process
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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.
Approved medicines with mapped indications
Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.
Broader indication categories (1)Hide
Broad umbrella indications (e.g. “Neoplasms”). Shown here because every medicine also appears under a more specific disease above — kept for completeness, de-emphasised for clarity.
Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.
Drugs targeting this protein
How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.
Niemann-Pick C1-like protein 1 inhibitor
Indicated for Hypercholesterolemia, Hyperlipidemias, Hyperlipoproteinemia Type II, Cardiovascular Diseases
ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.
Translational evidence
Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.
Strongest disease associations · via encoding gene NPC1L1
Gene-level evidence surfaced through the gene NPC1L1that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.
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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 per-type scores above show the calculation.
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Drug development
1 compounds recorded · 1 approved
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Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.
Tractability
Small molecules — Strong
Antibodies — Emerging
Protein degraders — Emerging
View underlying tractability evidence (10)Hide
Raw Open Targets tractability assessment buckets, by modality.
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. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.
View all trials (26)Hide
ClinicalTrials.gov via the drug-target graph.
What's happening now
Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for a drug that targets this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.
- 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.
- 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.
- New publicationCombined effects of ezetimibe and phytosterols on cholesterol metabolism: a randomized, controlled feeding study in humans.
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.