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Protein / target

Leptin receptor

Encoded byLEPRP48357Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
1
Approved medicines
Open Targets target-level
View by indication →
23
Clinical trials
Small-molecule tractable
Druggability
Structure with Ligand

Protein at a glance

Biological role

Transmembrane signaling receptor

Strongest disease association

Diabetes Mellitus, Type 2

Via encoding gene LEPR · Genetic evidence · score 0.80

Therapeutic position

Established drug target

Antibodies

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

Receptor for hormone LEP/leptin (Probable).

View complete UniProt function annotation

Receptor for hormone LEP/leptin (Probable) (PubMed:22405007). On ligand binding, mediates LEP central and peripheral effects through the activation of different signaling pathways such as JAK2/STAT3 and MAPK cascade/FOS. In the hypothalamus, LEP acts as an appetite-regulating factor that induces a decrease in food intake and an increase in energy consumption by inducing anorexinogenic factors and suppressing orexigenic neuropeptides, also regulates bone mass and secretion of hypothalamo-pituitary-adrenal hormones (By similarity) (PubMed:9537324). In the periphery, increases basal metabolism, influences reproductive function, regulates pancreatic beta-cell function and insulin secretion, is pro-angiogenic and affects innate and adaptive immunity (PubMed:12504075, PubMed:25060689, PubMed:8805376). Control of energy homeostasis and melanocortin production (stimulation of POMC and full repression of AgRP transcription) is mediated by STAT3 signaling, whereas distinct signals regulate NPY and the control of fertility, growth and glucose homeostasis. Involved in the regulation of counter-regulatory response to hypoglycemia by inhibiting neurons of the parabrachial nucleus. Has a specific effect on T lymphocyte responses, differentially regulating the proliferation of naive and memory T -ells. Leptin increases Th1 and suppresses Th2 cytokine production (By similarity)

Subcellular location

Cell membraneBasolateral cell membraneSecreted
Domains and Gene Ontology detail (37)

Domains & features

Fibronectin type-III 1Ig-likeFibronectin type-III 2Fibronectin type-III 3Fibronectin type-III 4

Gene Ontology

  • Cbasolateral plasma membrane
  • Cexternal side of plasma membrane
  • Cextracellular region
  • Cplasma membrane
  • Creceptor complex
  • Fcytokine binding
  • Fcytokine receptor activity
  • Fidentical protein binding
  • Fleptin receptor activity
  • Fpeptide hormone binding
  • Ftransmembrane signaling receptor activity
  • Pangiogenesis

1165 aa · 132 kDa · 5 isoforms

Biological roles

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

Cell proliferation & survivalGOImmune signallingUniProt · GO
View supporting evidence

Cell proliferation & survival

  • ·positive regulation of cell population proliferation

Immune signalling

  • ·Receptor for hormone LEP/leptin (Probable) (PubMed:22405007). On ligand binding, mediate…
  • ·cytokine binding
  • ·cytokine receptor activity
  • ·cytokine-mediated signaling pathway

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

Approved medicines with mapped indications

1 medicine · 2 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.

Lipodystrophy1 medicine
Liver Diseases1 medicine

Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

2

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.

metreleptin
Narrow target profileApprovedAgonist

Leptin receptor agonist

Indicated for Lipodystrophy, Liver Diseases

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

Mibavademab
Narrow target profilePhase 3Agonist

Leptin receptor agonist

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 LEPR

Gene-level evidence surfaced through the gene LEPR that 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.

Obesity disorder
0.84Well supported

Genetic evidence dominant · Open Targets 0.43

Diabetes Mellitus, Type 2
0.82Well supported

Genetic evidence dominant · Open Targets 0.51

Diabetes Mellitus
0.79Well supported

Genetic evidence dominant · Open Targets 0.43

Lipodystrophy
0.66Moderately supported

Clinical evidence dominant · Open Targets 0.54

Liver Diseases
0.46Limited support

Clinical evidence dominant · Open Targets 0.37

View evidence synthesis (5)
Obesity disorderWell supported
0.84
agreement 0.750.94
Genetic39%Clinical26%Animal model26%Literature10%

Open Targets aggregate 0.43 · 4 independent evidence families

Diabetes Mellitus, Type 2Well supported
0.82
agreement 0.720.93
Genetic85%Literature15%Clinical1%

Open Targets aggregate 0.51 · 3 independent evidence families

Diabetes MellitusWell supported
0.79
agreement 0.690.88
Genetic39%Clinical35%Animal model19%Literature7%

Open Targets aggregate 0.43 · 4 independent evidence families

LipodystrophyModerately supported
0.66
agreement 0.510.82
Clinical99%Literature1%

Open Targets aggregate 0.54 · 2 independent evidence families

Liver DiseasesLimited support
0.46
agreement 0.310.62
Clinical97%Literature3%

Open Targets aggregate 0.37 · 2 independent evidence families

This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. 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
Lipodystrophy0.54
Diabetes Mellitus, Type 20.51
Obesity disorder0.43
Diabetes Mellitus0.43
Liver Diseases0.37

Drug development

2 compounds recorded · 1 approved · 1 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 2 drugs that target 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 (2)
MIBAVADEMABPhase 3
METRELEPTINApproval

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 moleculesEmerging

Feasibility evidence (structure with ligand) — no clinical-stage drug of this modality recorded.

AntibodiesStrong

Advanced Clinical and UniProt loc high conf support this modality.

Protein degradersEmerging

Feasibility evidence (database ubiquitination) — no clinical-stage drug of this modality recorded.

Other modalitiesStrong

Approved Drug support this modality.

View underlying tractability evidence (8)
SM · Structure with LigandAB · Advanced ClinicalAB · UniProt loc high confAB · UniProt loc med confAB · UniProt SigP or TMHMMAB · GO CC med confPR · Database UbiquitinationOC · Approved Drug

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

weight gainClinPGx

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.

Clinical trials

23

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 (19)

ACTIVE_NOT_RECRUITING · via metreleptin · NCT02262806

ACTIVE_NOT_RECRUITING · via metreleptin · NCT00085982

COMPLETED · via metreleptin · NCT00596934

COMPLETED · via metreleptin · NCT00025883

ClinicalTrials.gov via the drug-target graph.

What's happening now

2

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 2 drugs that target 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. Trial status changed2026-07-29

    A Single-Arm, Open-Label, Safety Study in Patients With Generalized Lipodystrophy Switching From Metreleptin to Mibavademab, A Leptin Receptor Agonist Antibody

    Status changed to Completed · ClinicalTrials.gov · via Mibavademab

  2. Regulatory approval2018-07-30

    Approval: Myalepta (EMA)

    ema · regulatory · ema · via metreleptin

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.