RPL8 — Ribosomal Protein L8

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RPL8 — Ribosomal Protein L8

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RPL8 — Ribosomal Protein L8

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">RPL8 — Ribosomal Protein L8</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td>RPL8</td>
</tr>
<tr>
<td class="label">Name</td>
<td>Ribosomal Protein L8</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>8q24.3</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>6136</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P62917</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000126267</td>
</tr>
<tr>
<td class="label">Gene Type</td>
<td>Protein-coding</td>
</tr>
<tr>
<td class="label">Aliases</td>
<td>L8, SA-1, RL8</td>
</tr>
<tr>
<td class="label">Interactor</td>
<td>Function</td>
</tr>
<tr>
<td class="label">RPL5</td>
<td>60S subunit assembly</td>
</tr>
<tr>
<td class="label">RPL11</td>
<td>60S subunit assembly, ribosome biogenesis</td>
</tr>
<tr>
<td class="label">RPL23</td>
<td>Ribosomal stability</td>
</tr>
<tr>
<td class="label">RPL3</td>
<td>Peptidyl transferase activity</td>
</tr>
<tr>
<td class="label">eEF-1α</td>
<td>Translation elongation</td>
</tr>
<tr>
<td class="label">eEF-2</td>
<td>Translation elongation</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

Introduction

...

RPL8 — Ribosomal Protein L8

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">RPL8 — Ribosomal Protein L8</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td>RPL8</td>
</tr>
<tr>
<td class="label">Name</td>
<td>Ribosomal Protein L8</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>8q24.3</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>6136</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P62917</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000126267</td>
</tr>
<tr>
<td class="label">Gene Type</td>
<td>Protein-coding</td>
</tr>
<tr>
<td class="label">Aliases</td>
<td>L8, SA-1, RL8</td>
</tr>
<tr>
<td class="label">Interactor</td>
<td>Function</td>
</tr>
<tr>
<td class="label">RPL5</td>
<td>60S subunit assembly</td>
</tr>
<tr>
<td class="label">RPL11</td>
<td>60S subunit assembly, ribosome biogenesis</td>
</tr>
<tr>
<td class="label">RPL23</td>
<td>Ribosomal stability</td>
</tr>
<tr>
<td class="label">RPL3</td>
<td>Peptidyl transferase activity</td>
</tr>
<tr>
<td class="label">eEF-1α</td>
<td>Translation elongation</td>
</tr>
<tr>
<td class="label">eEF-2</td>
<td>Translation elongation</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

Introduction

RPL8 (Ribosomal Protein L8) encodes a component of the large 60S ribosomal subunit. While ribosomal proteins were historically considered mere structural components of the translation machinery, recent research has revealed that RPL8, like many other ribosomal proteins, participates in diverse cellular processes beyond canonical protein synthesis. RPL8 has been implicated in the pathogenesis of several neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD), where ribosomal dysfunction is increasingly recognized as a key pathological feature.

The ribosomal protein L8 is highly conserved across species and is essential for cell viability. Its expression is altered in various disease states, making it a potential biomarker and therapeutic target. Within the brain, RPL8 is expressed in regions critical for learning and memory, including the [hippocampus](/brain-regions/hippocampus), [cortex](/brain-regions/cortex), and [cerebellum](/brain-regions/cerebellum), as well as in the [substantia nigra](/brain-regions/substantia-nigra), which is particularly vulnerable in Parkinson's disease.

Gene Function

Core Ribosomal Function

RPL8 encodes Ribosomal Protein L8, a component of the large (60S) ribosomal subunit. The protein is located in the cytoplasm and plays a critical role in protein synthesis by forming part of the peptidyl transferase center (PTC) within the ribosome. As a ribosomal protein, RPL8 contributes to the structural integrity of the ribosome and participates in the catalysis of peptide bond formation during translation.

The ribosomal machinery is essential for all cellular protein synthesis. Ribosomes consist of two subunits: the small 40S subunit handles mRNA reading, while the large 60S subunit catalyzes peptide bond formation. RPL8 is one of approximately 47 proteins that comprise the eukaryotic 60S subunit, working in concert with rRNA molecules to maintain ribosomal function.

Structural Role in the 60S Subunit

RPL8 is positioned in the GTPase center region of the 60S ribosomal subunit, where it interacts with various translation factors. The protein contains an N-terminal domain that extends into the peptidyl transferase center and a C-terminal domain that participates in inter-subunit bridge formation. These structural features allow RPL8 to facilitate communication between the ribosomal subunits during the translation cycle.

Extra-Ribosomal Functions

Beyond its canonical role in translation, RPL8 has been implicated in several extra-ribosomal functions:

Gene Expression Regulation: RPL8 can function as a transcription factor, binding to specific DNA sequences and modulating the expression of genes involved in cell survival and stress responses.

Cell Cycle Control: Studies have shown that RPL8 interacts with cell cycle regulators and can influence cell proliferation in various cell types.

Apoptosis Regulation: RPL8 has been reported to interact with key apoptotic proteins, including p53, suggesting a role in programmed cell death decisions.

Stress Response: RPL8 participates in cellular stress responses, including oxidative stress and endoplasmic reticulum stress, which are relevant to neurodegeneration.

Ribosome-Associated Quality Control: RPL8 contributes to the monitoring of translational fidelity and the degradation of erroneous proteins, which is essential for neuronal homeostasis.

Expression Pattern

RPL8 is ubiquitously expressed throughout the body, including all brain regions. In the brain, expression is particularly high in:

Cerebral cortex: High metabolic demand requires robust protein synthesis
Hippocampus: Essential for synaptic plasticity and memory formation
Cerebellum: Critical for motor coordination and learning
Substantia nigra: High protein turnover in dopaminergic neurons
Basal ganglia: Involved in motor control and habit formation

Within neurons, RPL8 is expressed in:

Cell body (soma): Primary site of ribosomal protein synthesis
Dendrites: Local translation supports synaptic plasticity
Axons: Protein synthesis required for axon maintenance and regeneration
Synapses: Activity-dependent protein synthesis underlies learning and memory

Role in Neurodegeneration

Ribosomal Dysfunction in Alzheimer's Disease

Ribosomal dysfunction has emerged as a significant contributor to Alzheimer's disease (AD) pathogenesis. Multiple studies have documented reduced ribosomal RNA and protein levels in AD brain tissue, particularly in the hippocampus and cerebral cortex—regions most vulnerable to neurodegeneration. The impairment of ribosomal function leads to:

Global translation deficits: Reduced protein synthesis capacity in neurons compromises their ability to maintain proteostasis
Selective translation failure: While some essential proteins may still be translated, stress-responsive and synaptic proteins are disproportionately affected
Ribosomal stall: Misfolded proteins and stress conditions can cause ribosomal stalling, leading to ribosomal accumulation in stress granules

Specific mechanisms linking RPL8 to AD include:

Translation impairment correlating with cognitive decline
Amyloid-β peptides directly inhibiting ribosomal function
Tau pathology disrupting ribosomal function
ER stress activating RPL8-mediated apoptotic pathways

Ribosomal Dysfunction in Parkinson's Disease

In Parkinson's disease (PD), ribosomal abnormalities contribute to dopaminergic neuron vulnerability. The progressive loss of dopaminergic neurons in the substantia nigra pars compacta is associated with impaired protein quality control mechanisms. Key connections include:

Alpha-synuclein translation: Ribosomal proteins may interact with alpha-synuclein aggregation pathways
Mitochondrial stress response: Ribosomal dysfunction exacerbates mitochondrial defects common in PD
LRRK2 interactions: Mutations in LRRK2 (a key PD gene) may affect ribosomal translation fidelity
Neuroinflammation: Inflammatory cytokines alter ribosomal protein expression

Other Neurodegenerative Conditions

RPL8 alterations have been documented in:

Amyotrophic Lateral Sclerosis (ALS): RPL8 participates in stress granule formation and TDP-43 pathology affects ribosomal function
Huntington's Disease: Transcriptional dysregulation of ribosomal proteins
Frontotemporal Dementia: Altered ribosomal protein expression patterns
Multiple Sclerosis: Dysregulated ribosomal protein expression in demyelinating lesions
Prion Diseases: Ribosomal dysfunction in prion-infected neurons

Protein-Protein Interactions

Translation Machinery

RPL8 interacts with numerous ribosomal and non-ribosomal proteins:

Non-Ribosomal Interactions

c-Myc: Transcription factor that regulates RPL8 expression
p53: RPL8 can influence p53 stability through MDM2 interactions
Akt/mTOR pathway: Growth signaling modulates ribosomal biogenesis

Therapeutic Implications

Targeting Ribosomal Dysfunction

Modulating ribosomal function represents a potential therapeutic approach for neurodegenerative diseases:

Proteostasis restoration: Enhancing ribosomal function may restore protein synthesis capacity

Stress granule modulation: Reducing pathological stress granule formation

Synaptic protein synthesis: Improving translation of synaptic proteins critical for neuronal function

Small Molecule Approaches

Rapamycin/mTOR inhibitors: Modulate translational capacity
Ribosome-targeted compounds: Enhance ribosomal assembly or function
Antisense oligonucleotides: Modulate ribosomal protein expression
Translation enhancers: Compounds that improve ribosomal activity

Mermaid Diagram: Ribosomal Dysfunction in Neurodegeneration

Mermaid diagram (expand to render)

Gene Variants and Polymorphisms

While RPL8 is not a major disease-causing gene in neurodegeneration, several polymorphisms and variants have been studied:

Single Nucleotide Polymorphisms (SNPs): Various SNPs in the RPL8 gene region have been examined for association with neurodegenerative diseases

Copy Number Variations: Copy number variations involving RPL8 have been reported in various cancers

Expression Quantitative Trait Loci (eQTLs): eQTLs for RPL8 are associated with brain aging

Rare Variants: Whole-exome sequencing studies have identified rare RPL8 variants

Research Directions

Key areas of ongoing research include:

Mechanistic Studies: Elucidating the exact mechanisms by which RPL8 contributes to neuronal survival and dysfunction

Therapeutic Targeting: Developing small molecules that can modulate RPL8 function or expression

Biomarker Development: Using RPL8 as a diagnostic or prognostic biomarker

Stem Cell Models: Using iPSC-derived neurons to study RPL8 function in disease models

Ribosome Quality Control: Understanding how RPL8 contributes to ribosome-associated quality control

Clinical Relevance

Biomarker Potential

Alterations in ribosomal protein expression, including RPL8, may serve as biomarkers for neurodegenerative disease progression:

Decreased ribosomal protein expression in AD brains correlates with disease severity
Cerebrospinal fluid ribosomal protein levels may reflect neuronal health
Blood-based ribosomal markers are being investigated for early detection

Genetic Associations

While RPL8 itself is not a high-penetrance neurodegeneration gene, ribosomal protein genes collectively show:

Dysregulation in multiple neurodegenerative conditions
Expression quantitative trait loci (eQTLs) associated with disease risk
Interactions with known disease genes in proteostasis networks

References

[Wool, 1996 - Ribosomal proteins: structure, function, and evolution](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3411783/)

[Nierhaus, 1991 - The function of the ribosomal proteins](https://pubmed.ncbi.nlm.nih.gov/1848258/)

[Ban et al., 2014 - Structure of the eukaryotic ribosome at 3.0 Å](https://pubmed.ncbi.nlm.nih.gov/25494364/)

[Ding et al., 2005 - Ribosomal protein changes in Alzheimer's disease](https://pubmed.ncbi.nlm.nih.gov/15872108/)

[Wolozin & Ivanov, 2019 - Stress granules and neurodegeneration](https://pubmed.ncbi.nlm.nih.gov/30650977/)

[Bendotti et al., 2020 - Mitochondrial dysfunction and proteostasis in Parkinson's disease](https://pubmed.ncbi.nlm.nih.gov/32093456/)

[Cookson, 2010 - The role of LRRK2 in Parkinson's disease](https://pubmed.ncbi.nlm.nih.gov/20082902/)

[Mandelkow & Mandelkow, 2012 - Tau physiology and pathology](https://pubmed.ncbi.nlm.nih.gov/22391074/)

[Hernandez et al., 2020 - Ribosomal protein alterations in neurodegenerative diseases](https://pubmed.ncbi.nlm.nih.gov/32251627/)

[Rossi et al., 2020 - Proteostasis failure in neurodegeneration](https://pubmed.ncbi.nlm.nih.gov/32344829/)

[Kuroda et al., 2011 - Global analysis of ribosomal protein mRNA expression in AD](https://pubmed.ncbi.nlm.nih.gov/21253766/)

[Thams et al., 2019 - Cap-dependent translation inhibition in neurodegeneration](https://pubmed.ncbi.nlm.nih.gov/31305814/)

[Hegde et al., 2020 - Mitochondrial ribosomal proteins in neurodegeneration](https://pubmed.ncbi.nlm.nih.gov/32958732/)

[Yoshikawa et al., 2019 - eIF2α phosphorylation and translation control in AD](https://pubmed.ncbi.nlm.nih.gov/31130267/)

[Kim et al., 2021 - Stress granules in tauopathies](https://pubmed.ncbi.nlm.nih.gov/33760408/)

[Li et al., 2020 - Ribosome biogenesis in neural stem cells and neurodegeneration](https://pubmed.ncbi.nlm.nih.gov/32857462/)

[Schmid & Dreyfuss, 2021 - Targeting RNA metabolism in neurodegenerative diseases](https://pubmed.ncbi.nlm.nih.gov/33856304/)

[Xu et al., 2021 - Translation fidelity and neurodegeneration](https://pubmed.ncbi.nlm.nih.gov/34252789/)

[Grosely et al., 2022 - Ribosomal protein S6 kinase in cellular stress response](https://pubmed.ncbi.nlm.nih.gov/35178923/)

[Hernandez et al., 2020 - Ribosomal proteins in AD brain](https://pubmed.ncbi.nlm.nih.gov/32251627/)

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Related Entities

RPL8

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slug	genes-rpl8
kg_node_id	RPL8
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-76bc3f08a08b
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-rpl8'}
_schema_version	1

📊 Evidence Profile

Evidence Balance

+0%

Certainty

40%

Debates

0

Incoming

8

Outgoing

10

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

RPL8 — Ribosomal Protein L8

RPL8 — Ribosomal Protein L8

Overview

Introduction

RPL8 — Ribosomal Protein L8

Overview

Introduction

Gene Function

Core Ribosomal Function

Structural Role in the 60S Subunit

Extra-Ribosomal Functions

Expression Pattern

Role in Neurodegeneration

Ribosomal Dysfunction in Alzheimer's Disease

Ribosomal Dysfunction in Parkinson's Disease

Other Neurodegenerative Conditions

Protein-Protein Interactions

Translation Machinery

Non-Ribosomal Interactions

Therapeutic Implications

Targeting Ribosomal Dysfunction

Small Molecule Approaches

Mermaid Diagram: Ribosomal Dysfunction in Neurodegeneration

Gene Variants and Polymorphisms

Research Directions

Clinical Relevance

Biomarker Potential

Genetic Associations

See Also

References

💬 Discussion