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Protein / target

Sphingosine 1-phosphate receptor 5

Encoded byS1PR5Q9H228Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
6
Approved medicines
Open Targets target-level
View by indication →
2
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Sphingosine-1-phosphate receptor

Strongest disease association

Multiple Sclerosis

Via encoding gene S1PR5 · Genetic evidence · score 0.04

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

Receptor for the lysosphingolipid sphingosine 1-phosphate (S1P).

View complete UniProt function annotation

Receptor for the lysosphingolipid sphingosine 1-phosphate (S1P). S1P is a bioactive lysophospholipid that elicits diverse physiological effect on most types of cells and tissues. Is coupled to both the G(i/0)alpha and G(12) subclass of heteromeric G proteins (By similarity). May play a regulatory role in the transformation of radial glial cells into astrocytes and may affect proliferative activity of these cells

Subcellular location

Cell membrane
Domains and Gene Ontology detail (6)

Gene Ontology

  • Ccytoplasm
  • Cplasma membrane
  • Cpresynapse
  • FG protein-coupled receptor activity
  • Fsphingosine-1-phosphate receptor activity
  • Padenylate cyclase-activating G protein-coupled receptor signaling pathway

398 aa · 42 kDa · 2 isoforms

Biological roles

Reactome v97

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

Lipid & lipoprotein metabolismUniProtG protein-coupled signallingGO
View supporting evidence

Lipid & lipoprotein metabolism

  • ·Receptor for the lysosphingolipid sphingosine 1-phosphate (S1P). S1P is a bioactive lyso…

G protein-coupled signalling

  • ·G protein-coupled receptor activity
  • ·adenylate cyclase-activating G protein-coupled receptor signaling pathway
View underlying pathways (2)

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.

GNAI1GNA12SPHK1GNA13GNAI2GNAI3SPHK2GNG2GNB1KLRD1S1PR5

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 · 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.

Multiple Sclerosis1 medicine
Multiple Sclerosis, Relapsing-Remitting1 medicine

6 medicines meet Open Targets' target-level approved-medicine definition; the 1 shown here are those on this page with a canonical approved disease indication in the graph. 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.

Sphingosine 1-phosphate receptor agonist

Indicated for Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting

Acts on a complex — shared with S1PR2, S1PR4, S1PR3 +1 more · 1 of 5 recorded protein targets

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 S1PR5

Gene-level evidence surfaced through the gene S1PR5 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.

Multiple Sclerosis
0.75Well supported

Clinical evidence dominant · Open Targets 0.61

Colitis, Ulcerative
0.71Moderately supported

Clinical evidence dominant · Open Targets 0.57

Multiple Sclerosis, Relapsing-Remitting
0.62Moderately supported

Clinical evidence dominant · Open Targets 0.50

Crohn's Disease
0.48Limited support

Clinical evidence dominant · Open Targets 0.38

Carcinoma, Non-Small-Cell Lung
0.34Limited support

Clinical evidence dominant · Open Targets 0.28

View evidence synthesis (5)
Multiple SclerosisWell supported
0.75
agreement 0.650.86
Clinical94%Genetic6%Literature1%

Open Targets aggregate 0.61 · 3 independent evidence families

Colitis, UlcerativeModerately supported
0.71
agreement 0.610.82
Clinical90%Genetic5%RNA expression4%Literature1%

Open Targets aggregate 0.57 · 4 independent evidence families

Multiple Sclerosis, Relapsing-RemittingModerately supported
0.62
agreement 0.470.78
Clinical99%Literature1%

Open Targets aggregate 0.50 · 2 independent evidence families

Crohn's DiseaseLimited support
0.48
agreement 0.320.63
Clinical100%RNA expression0%

Open Targets aggregate 0.38 · 2 independent evidence families

Carcinoma, Non-Small-Cell LungLimited support
0.34
agreement 0.190.50
Clinical99%Literature1%

Open Targets aggregate 0.28 · 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
Multiple Sclerosis0.61
Colitis, Ulcerative0.57
Multiple Sclerosis, Relapsing-Remitting0.50
Crohn's Disease0.38
Carcinoma, Non-Small-Cell Lung0.28

Drug development

8 compounds recorded · 6 approved · 2 in clinical development

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 (8)
FINGOLIMOD HYDROCHLORIDEApproval
ETRASIMODApproval
OZANIMODApproval
ETRASIMOD ARGININEApproval
FINGOLIMOD LAURYL SULFATEApproval
FINGOLIMODApproval
AMISELIMOD HYDROCHLORIDEPhase 2
AMISELIMODPhase 2

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

Protein degradersEmerging

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

View underlying tractability evidence (8)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMMPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Clinical trials

2

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.

COMPLETED · via Fingolimod Hydrochloride · NCT03941743

COMPLETED · via Fingolimod Hydrochloride · NCT03943498

ClinicalTrials.gov via the drug-target graph.

What's happening now

3

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 publication2023-09-05
    Glial Sphingosine-Mediated Epigenetic Regulation Stabilizes Synaptic Function in <i>Drosophila</i> Models of Alzheimer's Disease.

    The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023 · 8 citations · Europe PMC · via Fingolimod Hydrochloride

  2. Regulatory approval2020-06-25

    Approval: Fingolimod Accord (EMA)

    ema · regulatory · ema · via Fingolimod Hydrochloride

  3. Regulatory approval2011-03-17

    Approval: Gilenya (EMA)

    ema · regulatory · ema · via Fingolimod Hydrochloride

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.