TMEM135 Gene
Overview
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">TMEM135 Gene</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>TMEM135</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>TMEM135</td>
</tr>
<tr>
<td class="label">Type</td>
<td>Gene</td>
</tr>
<tr>
<td class="label">NCBI</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/?term=TMEM135" target="_blank">Search NCBI</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
TMEM135 encodes a transmembrane protein linked to mitochondrial and peroxisomal biology. Emerging data indicate that TMEM135 participates in organelle remodeling, especially programs that coordinate mitochondrial fission and peroxisome-linked metabolic adaptation.[@lobo2021][@huang2023][@park2024] Compared with canonical neurodegeneration genes, TMEM135 evidence is still early and mechanistically focused.
The current best-supported interpretation is that TMEM135 is a stress-responsive regulator of organelle homeostasis whose dysfunction can alter bioenergetic resilience. That places it in pathways relevant to [Parkinson's disease](/diseases/parkinsons-disease), [Alzheimer's disease](/diseases/alzheimers-disease), and other disorders where mitochondrial quality control fails.
Molecular And Cellular Biology
Organelle Positioning And Remodeling
...TMEM135 Gene
Overview
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">TMEM135 Gene</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>TMEM135</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>TMEM135</td>
</tr>
<tr>
<td class="label">Type</td>
<td>Gene</td>
</tr>
<tr>
<td class="label">NCBI</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/?term=TMEM135" target="_blank">Search NCBI</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
TMEM135 encodes a transmembrane protein linked to mitochondrial and peroxisomal biology. Emerging data indicate that TMEM135 participates in organelle remodeling, especially programs that coordinate mitochondrial fission and peroxisome-linked metabolic adaptation.[@lobo2021][@huang2023][@park2024] Compared with canonical neurodegeneration genes, TMEM135 evidence is still early and mechanistically focused.
The current best-supported interpretation is that TMEM135 is a stress-responsive regulator of organelle homeostasis whose dysfunction can alter bioenergetic resilience. That places it in pathways relevant to [Parkinson's disease](/diseases/parkinsons-disease), [Alzheimer's disease](/diseases/alzheimers-disease), and other disorders where mitochondrial quality control fails.
Molecular And Cellular Biology
Organelle Positioning And Remodeling
Recent studies describe TMEM135 as a connector between peroxisomal state and mitochondrial fission behavior.[@huang2023][@park2024] In systems with high oxidative load, this coupling may influence fatty-acid handling, redox state, and ATP sufficiency.
Bioenergetic Adaptation
Work across metabolic and sensory models suggests TMEM135 levels can shift with cellular stress and alter downstream mitochondrial phenotype, including morphology and respiration-linked programs.[@lobo2021][@li2025] While tissue context differs, these observations support a conserved role in organelle adaptation.
Relationship To Known Neurodegeneration Axes
TMEM135 biology intersects conceptually with pathways involving [PINK1](/genes/pink1), [PRKN](/genes/prkn), [MFN2](/genes/mfn2), and [DNM1L](/genes/dnm1l), though direct causal ordering remains unresolved. Current evidence supports placing TMEM135 as a modifier node rather than a master upstream controller.[@lobo2021][@huang2023]
Relevance To Neurodegenerative Disease
Plausibility In Parkinsonian And Tauopathy States
Neurodegeneration frequently includes mitochondrial fragmentation, impaired mitophagy, and altered lipid handling. Because TMEM135 is linked to mitochondrial-peroxisomal coordination, it is biologically plausible that dysregulated TMEM135 signaling could amplify neuronal stress under these conditions.[@lobo2021][@park2024]
Human Disease Signal
A recent human mutation report connected TMEM135 to progressive sensorineural hearing loss, providing evidence that TMEM135 dysfunction can produce clinically meaningful neuronal phenotypes in humans.[@li2025] Although this is not a classical AD/PD phenotype, it strengthens confidence that TMEM135 is not merely a cell-culture artifact.
Evidence Limits
Direct large-cohort genetic association evidence for AD/PD risk is limited.
Most neurodegeneration-specific data are inferential (pathway overlap) rather than direct intervention studies.
Translational Considerations
Biomarker Potential
TMEM135 may be useful in multi-marker panels for mitochondrial/peroxisomal stress states, especially when interpreted with [mitochondrial dysfunction](/mechanisms/mitochondrial-dysfunction) and [oxidative stress](/mechanisms/oxidative-stress) signatures.[@lobo2021][@choi2025]
Therapeutic Positioning
At present, TMEM135 is a pathway-level discovery target. Practical near-term strategies include:
- Phenotypic screens in human iPSC [neurons](/entities/neurons) with TMEM135 perturbation under disease-relevant stressors.
- Combination studies with mitophagy and lipid-metabolism modulators.
- Multi-omic profiling to separate compensatory vs pathogenic TMEM135 changes.
Research Priorities
Define TMEM135 interaction partners in human neurons and glia under stress.
Quantify how TMEM135 perturbation shifts ATP production, [ROS](/entities/reactive-oxygen-species) balance, and axonal mitochondrial distribution.
Establish whether TMEM135 signatures track progression in longitudinal neurodegeneration cohorts.
Test whether TMEM135 modulation alters vulnerability in [tau](/proteins/tau)- and synuclein-based models.See Also
- [Parkinson's disease](/diseases/parkinsons-disease)
- [Alzheimer's disease](/diseases/alzheimers-disease)
- [mitochondrial dysfunction](/mechanisms/mitochondrial-dysfunction)
- [oxidative stress](/mechanisms/oxidative-stress)
External Links
- [NCBI Gene: PINK1](https://www.ncbi.nlm.nih.gov/gene/?term=PINK1)
- [GeneCards: PINK1](https://www.genecards.org/cgi-bin/carddisp.pl?gene=PINK1)
- [OMIM: PINK1](https://omim.org/search?search=PINK1)
- [Ensembl: PINK1](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=PINK1)
- [Allen Brain Atlas: PINK1](https://human.brain-map.org/microarray/search/show?search_term=PINK1)
References
[Lobo S, Chatterjee N, Kaur H, et al, TMEM135 is a regulator of mitochondrial dynamics and physiology (2021)](https://pubmed.ncbi.nlm.nih.gov/34359920/)
[Huang T, Xu M, Li Y, et al, TMEM135 links peroxisomes to regulation of mitochondrial fission and energy homeostasis (2023)](https://pubmed.ncbi.nlm.nih.gov/37773161/)
[Park S, Reynolds A, Wang M, Roles of TMEM135 in mitochondrial and peroxisomal function with implications for age-related retinal disease (2024)](https://pubmed.ncbi.nlm.nih.gov/38576540/)
[Li X, Qian J, Wu Y, et al, A TMEM135 mutation causes progressive sensorineural hearing loss (2025)](https://pubmed.ncbi.nlm.nih.gov/39970612/)
[Choi H, Reed T, Kim Y, TMEM135 deficiency improves steatosis through SIRT1-dependent metabolic reprogramming (2025)](https://pubmed.ncbi.nlm.nih.gov/39647810/)