Protein / target

Sphingosine 1-phosphate receptor 5

S1PR5Q9H228Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
6
Approved medicines
2
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Sphingosine-1-phosphate receptor activity

Strongest disease association

response to statin

Genetic evidence · score 0.35

Therapeutic maturity

Clinically validated target

6 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

6 approved · 2 in clinical development

2 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

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.

G protein-coupled signallingGOSynaptic signallingGO
View supporting evidence

G protein-coupled signalling

  • ·G protein-coupled receptor activity
  • ·adenylate cyclase-activating G protein-coupled receptor signaling pathway

Synaptic signalling

  • ·presynapse
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.

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.

Sphingosine 1-phosphate receptor agonist

Appears in clinical studies involving multiple sclerosis, relapsing-remitting multiple sclerosis, kidney transplant

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

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.

response to statin0.35

Genetic · overall 0.21

Abnormal nasolacrimal system morphology0.34

Genetic · overall 0.20

multiple sclerosis0.04

Genetic · overall 0.61

ulcerative colitis0.04

Genetic · overall 0.57

Highest-confidence therapeutic associations

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

relapsing-remitting multiple sclerosis0.83

Clinical · overall 0.50

Crohn disease0.63

Clinical · overall 0.38

primary progressive multiple sclerosis0.61

Clinical · overall 0.37

kidney transplant0.57

Clinical · overall 0.34

non-small cell lung carcinoma0.46

Clinical · overall 0.28

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

chronic inflammatory demyelinating polyradiculoneuropathy0.26

Clinical

Show all associations
multiple sclerosis0.61
ulcerative colitis0.57
relapsing-remitting multiple sclerosis0.50
Crohn disease0.38
primary progressive multiple sclerosis0.37
kidney transplant0.34
non-small cell lung carcinoma0.28
chronic inflammatory demyelinating polyradiculoneuropathy0.26
response to statin0.21
Abnormal nasolacrimal system morphology0.20

Open Targets ranks 170 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 · 8 total

FINGOLIMOD HYDROCHLORIDEApproval

multiple sclerosis · relapsing-remitting multiple sclerosis · kidney transplant

ETRASIMODApproval

ulcerative colitis · Crohn disease · atopic eczema

OZANIMODApproval

multiple sclerosis · non-small cell lung carcinoma · ulcerative colitis

ETRASIMOD ARGININEApproval

ulcerative colitis

FINGOLIMOD LAURYL SULFATEApproval

multiple sclerosis

FINGOLIMODApproval

primary progressive multiple sclerosis · multiple sclerosis · relapsing-remitting multiple sclerosis

AMISELIMOD HYDROCHLORIDEPhase 2

Crohn disease · multiple sclerosis · psoriasis

AMISELIMODPhase 2

ulcerative colitis · multiple sclerosis · systemic lupus erythematosus

Tractability

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

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.

COMPLETED · via Fingolimod Hydrochloride · NCT03943498

COMPLETED · via Fingolimod Hydrochloride · NCT03941743

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.

multiple sclerosisWell supported
0.75
agreement 0.650.86
Clinical94%Genetic6%Literature1%

Open Targets aggregate 0.61 · 3 independent evidence families

ulcerative colitisModerately supported
0.71
agreement 0.610.82
Clinical90%Genetic5%RNA expression4%Literature1%

Open Targets aggregate 0.57 · 4 independent evidence families

relapsing-remitting multiple sclerosisModerately supported
0.62
agreement 0.470.78
Clinical99%Literature1%

Open Targets aggregate 0.50 · 2 independent evidence families

Crohn diseaseLimited support
0.48
agreement 0.320.63
Clinical100%RNA expression0%

Open Targets aggregate 0.38 · 2 independent evidence families

primary progressive multiple sclerosisLimited support
0.46
agreement 0.290.62
Clinical100%

Open Targets aggregate 0.37 · 1 independent evidence family

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

3

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 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.