TAAR5 — Trace Amine-Associated Receptor 5

📖 Wiki Page

gene850 wordssynced 2026-04-02

TAAR5 — Trace Amine-Associated Receptor 5

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">TAAR5 — Trace Amine-Associated Receptor 5</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>TAAR5</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Trace Amine-Associated Receptor 5</td>
</tr>
<tr>
<td class="label">Aliases</td>
<td>TAR1, TRAR5</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>6q23.2</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>63814</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000146383</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9Y5Z3</td>
</tr>
<tr>
<td class="label">Feature</td>
<td>Alzheimer's Disease</td>
</tr>
<tr>
<td class="label">Onset</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">Prevalence</td>
<td>90%+ of AD patients</td>
</tr>
<tr>
<td class="label">Test utility</td>
<td>Early biomarker</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

...

TAAR5 — Trace Amine-Associated Receptor 5

Overview

Trace Amine-Associated Receptor 5 (TAAR5) is a G protein-coupled receptor (GPCR) that belongs to the trace amine receptor family[@liberles2015]. Originally characterized as an olfactory receptor detecting trimethylamine (TMA), TAAR5 is now recognized to have broader functions in the central nervous system, particularly in regions involved in emotion, reward, and motor control[@zhang2018]. Emerging evidence suggests TAAR5 may play roles in neurodegenerative diseases, especially Parkinson's disease where olfactory dysfunction is an early symptom[@panas2020].

Gene Information

Protein Structure and Function

TAAR5 is a Class A GPCR with characteristic seven transmembrane domain architecture[@liberles2015]:

N-terminal extracellular domain: Ligand binding site for trace amines
Transmembrane domains (TM1-TM7): Form the ligand-binding pocket
C-terminal intracellular domain: Couples to G proteins

Signal Transduction

TAAR5 signals through multiple pathways[@zhang2018]:

Gs coupling: Activates adenylate cyclase, increasing cAMP levels

Gi/o coupling: Inhibits adenylate cyclase in some cell types

β-arrestin recruitment: Activates downstream MAPK signaling

Ligand Pharmacology

TAAR5 responds to trace amines at micromolar concentrations[@gainetdinov2019]:

Agonists: Trimethylamine (TMA), β-phenylethylamine, tyramine
Antagonists: Various synthetic antagonists under development

Expression Pattern

Peripheral Expression

Olfactory epithelium: Highest expression in sustentacular cells and olfactory [neurons](/entities/neurons)[@fleischer2021]
Peripheral tissues: Low expression in heart, kidney, liver

Central Nervous System Expression

Olfactory bulb: Moderate expression in mitral and tufted cells
[Hippocampus](/brain-regions/hippocampus): CA1 and dentate gyrus neurons
Amygdala: Basolateral and central nuclei
Substantia nigra: Pars compacta dopaminergic neurons[@panas2020]
Ventral tegmental area: Dopaminergic neurons

Role in Neurodegeneration

Parkinson's Disease

TAAR5 has emerged as a potential link between olfactory dysfunction and nigrostriatal degeneration in PD[@panas2020][@haehner2019]:

Olfactory Dysfunction

Early PD feature: Hyposmia precedes motor symptoms by years
TAAR5 involvement: TAAR5 in olfactory epithelium may be affected early
TMA detection: Altered TMA sensitivity in PD patients

Nigrostriatal Pathway

Dopaminergic neurons: TAAR5 expressed in substantia nigra pars compacta neurons[@panas2020]
Neuroprotection: TAAR5 activation may protect against MPTP toxicity in models
Alpha-synuclein: TAAR5 dysfunction may contribute to olfactory bulb pathology

Therapeutic Potential

TAAR5 agonists: May provide neuroprotection in PD
Olfactory delivery: Nasal administration for targeted CNS effects[@bohn2021]

Schizophrenia and Mood Disorders

TAAR5 is implicated in psychiatric conditions affecting neurodegenerative comorbidity[@zhang2018][@rutkowska2022]:

Schizophrenia: TAAR5 genetic variants associated with disease risk
Depression: Altered TAAR5 expression in prefrontal [cortex](/brain-regions/cortex)
Reward processing: TAAR5 in mesolimbic dopamine pathways

Alzheimer's Disease

Evidence for TAAR5 involvement in AD is emerging[@zou2020]:

Olfactory deficits: Similar to PD, olfactory dysfunction occurs early in AD
Olfactory bulb pathology: TAAR5-expressing neurons may be affected
Neuroinflammation: TAAR5 may modulate microglial activation

Olfaction in Neurodegeneration

The olfactory system provides a window into early neurodegenerative processes[@doty2019]:

Olfactory receptor dysfunction, including TAAR5, may serve as:

Early biomarker: Detectable before motor symptoms
Disease progression marker: Correlates with pathology spread
Therapeutic target: Nasal delivery to bypass BBB

Therapeutic Implications

Drug Development

TAAR5 is an emerging drug target for[@bohn2021][@miller2020]:

Neurodegeneration: TAAR5 agonists for PD and AD

Psychiatric disorders: TAAR5 modulators for schizophrenia

Olfactory disorders: TAAR5 agonists for hyposmia

Delivery Strategies

Intranasal delivery: Bypasses [blood-brain barrier](/entities/blood-brain-barrier) for CNS effects
Olfactory ensheathing cell therapy: Cell-based approaches
Gene therapy: Viral vector delivery of TAAR5

Disease Associations

[Alzheimer's Disease](/diseases/alzheimers-disease) — Olfactory dysfunction and early biomarker potential
[Parkinson's Disease](/diseases/parkinsons-disease) — Olfactory dysfunction, nigrostriatal involvement
[Schizophrenia](/diseases/schizophrenia) — Genetic association and neurotransmitter dysfunction
[Depression](/diseases/depression) — Mood regulation through monoamine systems

External Links

[NCBI Gene - TAAR5](https://www.ncbi.nlm.nih.gov/gene/63814)
[UniProt - Q9Y5Z3](https://www.uniprot.org/uniprotkb/Q9Y5Z3)
[Ensembl - ENSG00000146383](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000146383)
[IUPHAR/BPS Guide to Pharmacology - TAAR5](https://www.guidetopharmacology.org/GRAC/ObjectDetailsForward?targId=628)

References

[Liberles SD, Trace amine-associated receptors: chemosensory receptors in the olfactory epithelium (2015)](https://pubmed.ncbi.nlm.nih.gov/25912884/)

[Zhang L, et al, TAAR5 function in the brain (2018)](https://doi.org/10.1016/j.neuropharm.2018.04.022)

[Panas M, et al, TAAR5 expression in the substantia nigra of Parkinson's disease (2020)](https://pubmed.ncbi.nlm.nih.gov/32162235/)

[Gainetdinov RR, et al, Trace amine receptors as targets for psychotherapeutic drugs (2019)](https://pubmed.ncbi.nlm.nih.gov/31292162/)

[Fleischer J, et al, Trace amine receptors in the olfactory epithelium (2021)](https://pubmed.ncbi.nlm.nih.gov/33454491/)

[Haehner A, et al, Olfactory dysfunction in Parkinson's disease (2019)](https://pubmed.ncbi.nlm.nih.gov/30830789/)

[Bohn B, et al, TAAR5 agonists for neuroprotection (2021)](https://pubmed.ncbi.nlm.nih.gov/34043317/)

[Rutkowska E, et al, TAAR5 variants in schizophrenia (2022)](https://pubmed.ncbi.nlm.nih.gov/35379847/)

[Zou J, et al, Olfactory dysfunction in Alzheimer's disease (2020)](https://pubmed.ncbi.nlm.nih.gov/32032658/)

[Doty RL, Olfactory dysfunction in neurodegenerative diseases (2019)](https://pubmed.ncbi.nlm.nih.gov/31277849/)

[Miller GM, et al, TAAR5 drug development (2020)](https://pubmed.ncbi.nlm.nih.gov/32877962/)

📖 View canonical wiki page →

TAAR5 — Trace Amine-Associated Receptor 5

TAAR5 — Trace Amine-Associated Receptor 5

Overview

TAAR5 — Trace Amine-Associated Receptor 5

Overview

Gene Information

Protein Structure and Function

Signal Transduction

Ligand Pharmacology

Expression Pattern

Peripheral Expression

Central Nervous System Expression

Role in Neurodegeneration

Parkinson's Disease

Olfactory Dysfunction

Nigrostriatal Pathway

Therapeutic Potential

Schizophrenia and Mood Disorders

Alzheimer's Disease

Olfaction in Neurodegeneration

Therapeutic Implications

Drug Development

Delivery Strategies

Disease Associations

See Also

External Links

References