<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">TMEM135 Protein</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>Protein</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/?query=TMEM135" target="_blank">Search UniProt</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
TMEM135 is a membrane-associated organelle regulator that links [mitochondrial dynamics](/mechanisms/mitochondrial-dynamics-pathway) and [peroxisomal dysfunction](/mechanisms/peroxisomal-dysfunction). Evidence in mammalian systems indicates that TMEM135 helps coordinate mitochondrial fission, peroxisome-related lipid processing, and energetic adaptation under cellular stress.
In NeuroWiki terms, TMEM135 is best viewed as a network-modulating protein rather than a primary monogenic driver of classic neurodegenerative syndromes. Current human disease associations are strongest in retina/hearing phenotypes and metabolic stress biology, while neurodegeneration relevance is mechanistically plausible but still early-stage.[@zhou2023][@nam2025]
<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">TMEM135 Protein</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>Protein</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/?query=TMEM135" target="_blank">Search UniProt</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
TMEM135 is a membrane-associated organelle regulator that links [mitochondrial dynamics](/mechanisms/mitochondrial-dynamics-pathway) and [peroxisomal dysfunction](/mechanisms/peroxisomal-dysfunction). Evidence in mammalian systems indicates that TMEM135 helps coordinate mitochondrial fission, peroxisome-related lipid processing, and energetic adaptation under cellular stress.
In NeuroWiki terms, TMEM135 is best viewed as a network-modulating protein rather than a primary monogenic driver of classic neurodegenerative syndromes. Current human disease associations are strongest in retina/hearing phenotypes and metabolic stress biology, while neurodegeneration relevance is mechanistically plausible but still early-stage.[@zhou2023][@nam2025]
TMEM135 is a multi-pass transmembrane protein localized to mitochondrial and peroxisome-associated membranes, where it influences organelle morphology and substrate flux.[@exil2021][@zaveri2025] Unlike catalytic enzymes, TMEM135 appears to function as an organizational or trafficking regulator inside the mitochondrial-peroxisome axis.[@exil2021][@zaveri2023]
Key context:
Experimental data support a role for TMEM135 in mitochondrial fission-state control and adaptation during energetic demand.[@exil2021][@zhou2023] This places TMEM135 upstream of mitochondrial quality-control logic that also intersects with [DRP1](/proteins/drp1-protein), [mitophagy](/mechanisms/mitophagy), and oxidative stress buffering pathways.[@gao2021][@giacomello2017]
TMEM135 participates in peroxisome-linked lipid handling, including pathways relevant to very-long-chain fatty acids and docosahexaenoic acid (DHA) balance in some systems.[@zaveri2023][@passmore2008] Because neuronal membranes are lipid-intensive and synaptic function is lipid-sensitive, disruption in peroxisomal support can have downstream CNS effects even when the initial defect is metabolic.[@passmore2008][@berger2013]
TMEM135 appears to act at an interface where mitochondrial and peroxisomal stress responses are coordinated.[@exil2021][@zaveri2023] This systems role may be more important than a single molecular interaction, particularly in aging tissues where cumulative oxidative and energetic stress rises.
Mitochondrial dysfunction is a convergent mechanism across [Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), and related [tau](/proteins/tau)/synuclein disorders.[@gao2021][@giacomello2017][@lin2006] TMEM135 does not yet have strong direct causal evidence in these diseases, but its mechanistic position is relevant because it influences the same organelle-control layer that fails in vulnerable [neurons](/entities/neurons).
Practical interpretation:
Several TMEM135 studies show retinal pathology and progressive hearing phenotypes in mutation models.[@nam2025][@lee2016] These findings are valuable for neurodegeneration research because retina and auditory pathways can serve as measurable windows into early bioenergetic and organelle dysfunction in aging brains.
TMEM135 has reproducible links to systemic metabolic phenotypes (hepatic lipid handling, adipose energy balance, and stress adaptation).[@zaveri2025][@zaveri2023][@arnold2018] Since metabolic syndrome and insulin resistance worsen risk trajectories in dementia and movement disorders, TMEM135 may be important in the metabolic amplification layer of neurodegeneration risk rather than as a direct trigger.[@lin2006][@arnold2018]
High-value next steps:
For NeuroWiki curation, TMEM135 is most useful when linked across: