Protein / target

NPC1-like intracellular cholesterol transporter 1

NPC1L1Q9UHC9Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
1
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Protein homodimerization activity

Primary system

Endocrine & metabolic

Strongest disease association

Hypercholesterolemia

Genetic evidence · score 0.77

Therapeutic maturity

Clinically validated target

1 approved medicine against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

1 approved

30 linked trials

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

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.

Metabolic enzyme activityGOMuscle contractionGO
View supporting evidence

Metabolic enzyme activity

  • ·lipoprotein metabolic process
  • ·vitamin E metabolic process

Muscle contraction

  • ·myosin V binding
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.

Drugs targeting this protein

1

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.

ezetimibe
Narrow target profileApprovedInhibitor

Niemann-Pick C1-like protein 1 inhibitor

Appears in clinical studies involving hyperlipidemia, Hypercholesterolemia, familial hypercholesterolemia, atherosclerosis

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

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

Translational evidence

Open Targets 26

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.

Hypercholesterolemia0.77

Genetic · overall 0.72

metabolic disease0.74

Genetic · overall 0.46

hyperlipidemia0.59

Genetic · overall 0.68

familial hypercholesterolemia0.53

Genetic · overall 0.63

Highest-confidence therapeutic associations

Diseases where a drug acting on this target has already reached clinical development.

inherited lipid metabolism disorder0.90

Clinical · overall 0.54

cardiovascular disorder0.86

Clinical · overall 0.53

atherosclerosis0.77

Clinical · overall 0.48

coronary artery disorder0.68

Clinical · overall 0.43

type 2 diabetes mellitus0.64

Clinical · overall 0.40

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

diabetes mellitus0.39

Clinical

Show all associations
Hypercholesterolemia0.72
hyperlipidemia0.68
familial hypercholesterolemia0.63
inherited lipid metabolism disorder0.54
cardiovascular disorder0.53
atherosclerosis0.48
metabolic disease0.46
coronary artery disorder0.43
type 2 diabetes mellitus0.40
diabetes mellitus0.39

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

EZETIMIBEApproval

hyperlipidemia · Hypercholesterolemia · familial hypercholesterolemia

Tractability

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

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.

Show remaining trials (24)

COMPLETED · via ezetimibe · NCT00701727

ClinicalTrials.gov via the drug-target graph.

Forefront confidence

Synthesis

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.

HypercholesterolemiaWell supported
0.94
agreement 0.841.00
Genetic50%Clinical48%Literature3%

Open Targets aggregate 0.72 · 3 independent evidence families

hyperlipidemiaWell 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 diseaseModerately 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

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

13

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.

  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. Convergence high2018-07-18

    Ezetimibe lowers LDL cholesterol in hyperlipidaemia — High confidence reached

    Independent evidence reached high confidence (79%, ±4%), up from moderate. Support spans 4 independent groups across 29 trials with a known outcome. · confidence · via ezetimibe

  7. Supplemental approval2018-05-21

    Supplemental approval: EZETIMIBE (ANDA209234)

    fda · regulatory · fda · via ezetimibe

  8. Regulatory approval2017-12-21

    Approval: EZETIMIBE (ANDA209234)

    fda · regulatory · fda · via ezetimibe

  9. 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

  10. 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

  11. 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

  12. 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

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.