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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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TSPO
translocator protein
Chromosome 22 · 22q13.2
NCBI Gene: 706Ensembl: ENSG00000100300.19HGNC: HGNC:1158UniProt: O76068
214PubMed Papers
20Diseases
3Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
ReceptorTransporter
RESEARCH IMPACT
Trending
CLINICAL
FDA Approved Target
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
mitochondrionprotein bindingextracellular exosomemembraneneurodegenerative diseaseAlzheimer diseaseanxiety disorderParkinson disease
✦AI Summary

TSPO (translocator protein) is a mitochondrial membrane protein with multifaceted physiological roles. Molecularly, TSPO functions as a cholesterol-dependent protoporphyrin IX oxygenase 1, binding cholesterol and porphyrins to facilitate their metabolism. The protein regulates cholesterol transport across mitochondrial membranes and influences cellular metabolism 2, though its contribution to steroid hormone biosynthesis appears minimal 2. TSPO was initially identified as a peripheral benzodiazepine receptor and binds various ligands including isoquinoline carboxamides. In pathophysiology, TSPO expression is markedly upregulated in brain injury, inflammation, and cancer 3. Critically, TSPO elevation correlates with microglial activation and neuroinflammation in neurodegenerative diseases 3. In Alzheimer's disease, TSPO is primarily expressed in phagocytic (CD68+) microglia, reflecting ongoing neurodegeneration 4. TSPO uptake correlates with amyloid-β deposition and cognitive decline 5. TSPO also responds to diverse stressors (psychological and physical) in psychiatric and stress-related disorders 6. Clinically, TSPO PET imaging serves as a valuable neuroinflammation biomarker 7, though limitations include lack of cellular specificity and inability to distinguish neuroprotective from neurotoxic inflammation. TSPO knockout studies confirm its essential role in mitochondrial respiration and cellular metabolism 2, establishing it as both a biomarker and potential therapeutic target for neuroinflammatory conditions.

Sources cited
1
TSPO functions as a cholesterol-dependent protoporphyrin IX oxygenase
PMID: 40146857
2
TSPO knockout alters mitochondrial membrane potential, calcium levels, and respiratory function; not required for steroid biosynthesis in microglia
PMID: 31323920
3
TSPO is upregulated in brain injury, inflammation, and cancer; correlates with microglial activation
PMID: 21498529
4
In Alzheimer's disease, TSPO is primarily expressed in phagocytic (CD68+) microglia reflecting neurodegeneration
PMID: 39540994
5
TSPO uptake correlates with amyloid-β deposition and cognitive decline in Alzheimer's disease
PMID: 37801139
6
TSPO is upregulated in microglia in response to diverse stressors in psychiatric and stress-related disorders
PMID: 32980493
7
TSPO PET is useful for imaging neuroinflammation in neurodegenerative disorders but lacks cellular specificity
PMID: 35649654
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.45Moderate
Alzheimer diseaseOpen Targets
0.40Weak
anxiety disorderOpen Targets
0.39Weak
Parkinson diseaseOpen Targets
0.38Weak
multiple sclerosisOpen Targets
0.38Weak
lysosomal storage diseaseOpen Targets
0.36Weak
neuroinflammatory disorderOpen Targets
0.25Weak
neoplasmOpen Targets
0.12Weak
gliomaOpen Targets
0.11Weak
breast cancerOpen Targets
0.11Weak
glioblastoma multiformeOpen Targets
0.11Weak
post-traumatic stress disorderOpen Targets
0.11Weak
glioblastomaOpen Targets
0.10Weak
irritable bowel syndromeOpen Targets
0.10Weak
SepsisOpen Targets
0.10Suggestive
hepatocellular carcinomaOpen Targets
0.10Suggestive
experimental autoimmune encephalomyelitisOpen Targets
0.10Suggestive
cancerOpen Targets
0.09Suggestive
strokeOpen Targets
0.09Suggestive
major depressive disorderOpen Targets
0.09Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets3
ALPIDEMApproved
Translocator protein partial agonist
anxiety disorder
EMAPUNILPhase II
Translocator protein agonist
anxiety disorder
ONO-2952Phase II
Translocator protein antagonist
irritable bowel syndrome
Related Genes
VDAC1Protein interaction100%TSPOAP1Protein interaction99%VDAC3Protein interaction96%BCL2Protein interaction96%SLC25A31Protein interaction96%VDAC2Protein interaction96%
Tissue Expression6 tissues
Lung
100%
Bone Marrow
80%
Ovary
27%
Liver
25%
Heart
18%
Brain
10%
Gene Interaction Network
Click a node to explore
TSPOVDAC1TSPOAP1VDAC3BCL2SLC25A31VDAC2
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt O76068
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.87LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.35 [0.91–1.87]
RankingsWhere TSPO stands among ~20K protein-coding genes
  • #1,944of 20,598
    Most Researched214 · top 10%
  • #858of 1,025
    FDA-Approved Drug Targets1
  • #17,026of 17,882
    Most Constrained (LOEUF)1.87
Genes detectedTSPO
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
The translocator protein.
PMID: 21498529
J Nucl Med · 2011
1.00
2
The microglial translocator protein (TSPO) in Alzheimer's disease reflects a phagocytic phenotype.
PMID: 39540994
Acta Neuropathol · 2024
0.90
3
Cholesterol-dependent enzyme activity of human TSPO1.
PMID: 40146857
Proc Natl Acad Sci U S A · 2025
0.80
4
A Systematic Review on Dementia and Translocator Protein (TSPO): When Nuclear Medicine Highlights an Underlying Expression.
PMID: 37189346
Biomolecules · 2023
0.76
5
Kinetic modeling and parameter estimation of TSPO PET imaging in the human brain.
PMID: 33693967
Eur J Nucl Med Mol Imaging · 2021
0.70