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Protein / target

NPC1-like intracellular cholesterol transporter 1

Encoded byNPC1L1Q9UHC9Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
1
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Protein homodimerization

Strongest disease association

Metabolic Diseases

Via encoding gene NPC1L1 · Genetic evidence · score 0.74

Therapeutic position

Established drug target

Small molecules

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Plays a major role in cholesterol homeostasis.

View complete UniProt function annotation

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

Apical cell membraneCell membraneCytoplasmic vesicle membrane
Domains and Gene Ontology detail (18)

Domains & features

SSD

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

1359 aa · 149 kDa · 4 isoforms

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Lipid & lipoprotein metabolismUniProt · GO
View supporting evidence

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
View underlying pathways (1)

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

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.

CYP7A1SCARB1HMGCRABCG5APOBABCG8SREBF2NPC2ABCA1APOA1NPC1L1

10 strongest partners — larger node and heavier line mean higher confidence

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

1 medicine · 4 areas

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.

Hypercholesterolemia1 medicine
Hyperlipidemias1 medicine
Hyperlipoproteinemia Type II1 medicine
Broader indication categories (1)
Cardiovascular Diseases1 medicine

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

1

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.

ezetimibe
Narrow target profileApprovedInhibitor

Niemann-Pick C1-like protein 1 inhibitor

Indicated for Hypercholesterolemia, Hyperlipidemias, Hyperlipoproteinemia Type II, Cardiovascular Diseases

Direct interaction with this protein · Only this protein recorded as a target

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

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.

Hyperlipidemias
0.89Well supported

Clinical evidence dominant · Open Targets 0.68

Familial hypercholesterolemia
0.85Well supported

Clinical evidence dominant · Open Targets 0.63

Metabolic Diseases
0.75Moderately supported

Genetic evidence dominant · Open Targets 0.46

Inherited lipid metabolism disorder
0.67Moderately supported

Clinical evidence dominant · Open Targets 0.54

Cardiovascular Diseases
0.65Moderately supported

Clinical evidence dominant · Open Targets 0.53

View evidence synthesis (5)
HyperlipidemiasWell supported
0.89
agreement 0.781.00
Clinical54%Genetic44%Literature2%

Open Targets aggregate 0.68 · 3 independent evidence families

Familial hypercholesterolemiaWell supported
0.85
agreement 0.740.96
Clinical54%Genetic42%Literature4%

Open Targets aggregate 0.63 · 3 independent evidence families

Metabolic DiseasesModerately supported
0.75
agreement 0.610.89
Genetic98%Literature2%

Open Targets aggregate 0.46 · 2 independent evidence families

Inherited lipid metabolism disorderModerately supported
0.67
agreement 0.520.83
Clinical100%Literature1%

Open Targets aggregate 0.54 · 2 independent evidence families

Cardiovascular DiseasesModerately supported
0.65
agreement 0.490.81
Clinical98%Literature2%

Open Targets aggregate 0.53 · 2 independent evidence families

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.

Show all associations
Hyperlipidemias0.68
Familial hypercholesterolemia0.63
Inherited lipid metabolism disorder0.54
Cardiovascular Diseases0.53
Atherosclerosis0.48
Metabolic Diseases0.46
Coronary Artery Disease0.43
Diabetes Mellitus, Type 20.40
Diabetes Mellitus0.39

Drug development

1 compounds recorded · 1 approved

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 1 drug that targets this protein in Forefront's canonical graph (1 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (1)
EZETIMIBEApproval

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 moleculesStrong

Approved Drug and Structure with Ligand support this modality.

AntibodiesEmerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

Feasibility evidence (half-life data and small molecule binder) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (10)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMMPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Clinical trials

30

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)

COMPLETED · via ezetimibe · NCT04369664

WITHDRAWN · via ezetimibe · NCT03750760

ClinicalTrials.gov via the drug-target graph.

What's happening now

12

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.

  1. New publication2025-05-07
    Fixed-dose combination of obicetrapib and ezetimibe for LDL cholesterol reduction (TANDEM): a phase 3, randomised, double-blind, placebo-controlled trial.

    Lancet (London, England) · 2025 · 31 citations · Europe PMC · via ezetimibe

  2. Label change2024-08-15

    Label change: EZETIMIBE (ANDA209234)

    fda · regulatory · fda · via ezetimibe

  3. Label change2024-06-17

    Label change: EZETIMIBE (ANDA209234)

    fda · regulatory · fda · via ezetimibe

  4. Label change2022-12-16

    Label change: EZETIMIBE (ANDA209234)

    fda · regulatory · fda · via ezetimibe

  5. New publication2022-11-06
    Small Interfering RNA to Reduce Lipoprotein(a) in Cardiovascular Disease.

    The New England journal of medicine · 2022 · 405 citations · Europe PMC · via ezetimibe

  6. Supplemental approval2018-05-21

    Supplemental approval: EZETIMIBE (ANDA209234)

    fda · regulatory · fda · via ezetimibe

  7. Regulatory approval2017-12-21

    Approval: EZETIMIBE (ANDA209234)

    fda · regulatory · fda · via ezetimibe

  8. New publication2017-08-01
    Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel.

    European heart journal · 2017 · 2,459 citations · Europe PMC · via ezetimibe

  9. New publication2015-06-03
    Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes.

    The New England journal of medicine · 2015 · 3,026 citations · Europe PMC · via ezetimibe

  10. New publication2015-05-01
    A randomized, double-blind, placebo-controlled study of the effect of ezetimibe on glucose metabolism in subjects with type 2 diabetes mellitus and hypercholesterolemia.

    Lipids in health and disease · 2015 · 15 citations · Europe PMC · via ezetimibe

  11. New publication2015-04-01
    Efficacy and safety of ezetimibe monotherapy in children with heterozygous familial or nonfamilial hypercholesterolemia.

    The Journal of pediatrics · 2015 · 47 citations · Europe PMC · via ezetimibe

  12. New publication2011-07-18
    Combined effects of ezetimibe and phytosterols on cholesterol metabolism: a randomized, controlled feeding study in humans.

    Circulation · 2011 · 46 citations · Europe PMC · via ezetimibe

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.