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plin3

<div class="infobox infobox-gene">
<h3>PLIN3</h3>
<table>
<tr><th>Full Name</th><td>Perilipin 3 (TIP47)</td></tr>
<tr><th>Chromosomal Location</th><td>19p13.3</td></tr>
<tr><th>NCBI Gene ID</th><td>[10226](https://www.ncbi.nlm.nih.gov/gene/10226)</td></tr>
<tr><th>OMIM</th><td>[604687](https://www.omim.org/entry/604687)</td></tr>
<tr><th>Ensembl ID</th><td>ENSG00000138326</td></tr>
<tr><th>UniProt</th><td>[O76014](https://www.uniprot.org/uniprot/O76014)</td></tr>
<tr><th>Protein Class</th><td>Perilipin family</td></tr>
<tr><th>Associated Diseases</th><td>Parkinson's Disease, Neurodegeneration with Brain Iron Accumulation (NBIA), Lysosomal Storage Disorders</td></tr>
</table>
</div>

Gene Overview

PLIN3 (Perilipin 3), also known as TIP47 (Tail-Interacting Protein of 47 kDa), encodes a lipid droplet-associated protein that plays crucial roles in lipid metabolism, autophagy regulation, and lysosomal function. Perilipins are a family of proteins (PLIN1-5) that coat the surface of lipid droplets, regulating their formation, size, and interaction with cellular trafficking pathways.

PLIN3 is unique among perilipins as it not only associates with lipid droplets but also participates in endosomal and lysosomal trafficking. This dual localization positions PLIN3 at the intersection of lipid metabolism and autophagy—two processes critical for neuronal survival. PLIN3 dysfunction has been implicated in Parkinson's disease, Alzheimer's disease, and other neurodegenerative disorders.

Function

Lipid Droplet Regulation

...

plin3

<div class="infobox infobox-gene">
<h3>PLIN3</h3>
<table>
<tr><th>Full Name</th><td>Perilipin 3 (TIP47)</td></tr>
<tr><th>Chromosomal Location</th><td>19p13.3</td></tr>
<tr><th>NCBI Gene ID</th><td>[10226](https://www.ncbi.nlm.nih.gov/gene/10226)</td></tr>
<tr><th>OMIM</th><td>[604687](https://www.omim.org/entry/604687)</td></tr>
<tr><th>Ensembl ID</th><td>ENSG00000138326</td></tr>
<tr><th>UniProt</th><td>[O76014](https://www.uniprot.org/uniprot/O76014)</td></tr>
<tr><th>Protein Class</th><td>Perilipin family</td></tr>
<tr><th>Associated Diseases</th><td>Parkinson's Disease, Neurodegeneration with Brain Iron Accumulation (NBIA), Lysosomal Storage Disorders</td></tr>
</table>
</div>

Gene Overview

PLIN3 (Perilipin 3), also known as TIP47 (Tail-Interacting Protein of 47 kDa), encodes a lipid droplet-associated protein that plays crucial roles in lipid metabolism, autophagy regulation, and lysosomal function. Perilipins are a family of proteins (PLIN1-5) that coat the surface of lipid droplets, regulating their formation, size, and interaction with cellular trafficking pathways.

PLIN3 is unique among perilipins as it not only associates with lipid droplets but also participates in endosomal and lysosomal trafficking. This dual localization positions PLIN3 at the intersection of lipid metabolism and autophagy—two processes critical for neuronal survival. PLIN3 dysfunction has been implicated in Parkinson's disease, Alzheimer's disease, and other neurodegenerative disorders.

Function

Lipid Droplet Regulation

PLIN3 is a fundamental regulator of lipid droplet biology:

Lipid Droplet Coat Function

As a lipid droplet-associated protein, PLIN3:

Coats lipid droplet surface: Forms a monomolecular layer on the droplet surface
Regulates size: Controls lipid droplet growth and coalescence
Prevents lipolysis: Protects stored triglycerides from ATGL-mediated hydrolysis
Recruits proteins: Attracts lipases and other regulatory proteins

Lipid Droplet Dynamics

| Function | Mechanism | Outcome |
|----------|-----------|---------|
| Formation | Nucleates lipid droplet biogenesis | New droplet creation |
| Growth | Allows lipid accumulation | Droplet expansion |
| Fusion | Mediates droplet contact | Size regulation |
| Turnover | Triggers lipolysis | Lipid mobilization |

Autophagy Regulation

PLIN3 plays a critical role in the intersection of lipid droplets and autophagy:

Lipophagy

PLIN3 is involved in lipophagy, the autophagic degradation of lipid droplets:

Lipid droplet recognition: PLIN3 marks droplets for selective autophagy
Autophagosome recruitment: Facilitates LC3 binding to lipid droplets
Lysosomal fusion: Coordinates droplet delivery to lysosomes
Lipid mobilization: Releases fatty acids during starvation

Interaction with Autophagy Machinery

| Autophagy Component | Interaction | Function |
|---------------------|------------|----------|
| LC3/GABARAP | Direct binding | Autophagosome recruitment |
| ATG14L | Coordinated regulation | Autophagosome formation |
| ULK1 | Phosphorylation | Initiation control |
| mTORC1 | Signaling integration | Nutrient sensing |

Lysosomal Function

PLIN3 participates in lysosomal pathways beyond lipid droplet regulation:

Endosomal Trafficking

Endosome maturation: Regulates endosomal cargo sorting
Lysosomal delivery: Directs proteins to lysosomal compartments
Membrane trafficking: Coordinates vesicle fusion events

Protein Interactions in Lysosomal Pathways

| Interactor | Function | Reference |
|------------|----------|-----------|
| Rab proteins | Vesicle trafficking | [@konige2014] |
| ESCRT complex | Cargo sorting | [@martens2012] |
| LAMP proteins | Lysosomal membrane | [@koga2019] |
| Cathepsins | Lysosomal enzymes | [@gandhi2020] |

Cellular Homeostasis

Beyond lipid droplets and autophagy, PLIN3 contributes to:

Lipid Metabolism

Fatty acid storage: Sequesters fatty acids in neutral lipids
Lipid signaling: Modulates lipid-derived signaling molecules
Energy homeostasis: Provides energy during fasting through β-oxidation

Mitochondrial Function

Fatty acid delivery: Delivers lipids to mitochondria for β-oxidation
Mitochondrial dynamics: Affects mitochondrial morphology
Oxidative stress: Modulates ROS production from lipid metabolism

Expression

Tissue Distribution

PLIN3 is expressed in various tissues with specific patterns:

Brain: Neurons (especially dopaminergic neurons), glia
Liver: Hepatocytes (highest expression)
Adipose tissue: Adipocytes
Muscle: Skeletal muscle fibers
Kidney: Renal tubules
Testis: Spermatogenic cells

Brain Expression

Within the brain, PLIN3 shows regional specificity:

| Region | Expression Level | Cell Type |
|--------|-----------------|-----------|
| Substantia Nigra | High | Dopaminergic neurons |
| Cerebral Cortex | High | Pyramidal neurons |
| Hippocampus | High | CA1-CA3 pyramidal cells |
| Basal Ganglia | Moderate | Medium spiny neurons |
| Cerebellum | Moderate | Purkinje cells |

Cellular Localization

PLIN3 localizes to multiple cellular compartments:

Lipid droplets: Primary surface localization
Endosomes: Cytoplasmic face
Lysosomes: Associated with membrane
Cytosol: Soluble pool
Mitochondria: Some isoforms

Regulation of Expression

PLIN3 expression is regulated by:

Nutritional status: Upregulated during lipid loading
Hormonal regulation: Insulin and glucocorticoids
Cellular stress: Oxidative stress response
Circadian rhythm: Diurnal expression patterns
Development: Tissue-specific developmental regulation

Disease Associations

Parkinson's Disease (PD)

PLIN3 has been strongly implicated in Parkinson's disease pathogenesis:

Genetic Evidence

GWAS associations: PLIN3 variants linked to PD risk
Expression studies: Altered PLIN3 levels in PD brains
Mutation effects: Pathogenic variants affect lipid droplet function

Mechanistic Links

| Mechanism | Effect of PLIN3 Dysfunction |
|-----------|----------------------------|
| α-Synuclein clearance | Impaired autophagic degradation |
| Lipid homeostasis | Disrupted neuronal lipid metabolism |
| Mitochondrial function | Altered fatty acid oxidation |
| Lysosomal function | Impaired lipophagy |

Lipid Droplet Accumulation

PD brains show:

Increased lipid droplet accumulation in dopaminergic neurons
PLIN3 redistribution in PD neurons
Correlation with α-synuclein pathology

Therapeutic Implications

Autophagy enhancers targeting lipophagy
Lipid metabolism modulators
Lysosomal function enhancers

Neurodegeneration with Brain Iron Accumulation (NBIA)

PLIN3 is involved in iron metabolism through lipid homeostasis:

Iron-Lipid Connection

Lipid droplet function: Iron handling requires proper lipid metabolism
Ferritin regulation: PLIN3 affects iron storage proteins
Oxidative stress: Iron-induced ROS from lipid peroxidation

NBIA Phenotypes

Iron accumulation in the brain
Lipid droplet abnormalities
Neurodegeneration with axonal spheroids

Alzheimer's Disease (AD)

PLIN3 contributes to Alzheimer's disease through several mechanisms:

Lipid Dysregulation

Altered lipid droplet metabolism in AD neurons
Changes in PLIN3 expression with disease progression
Correlation with amyloid and tau pathology

Autophagy Failure

Impaired lipophagy in AD neurons
Autophagosome accumulation
Reduced clearance of protein aggregates

Therapeutic Potential

PLIN3 modulators for lipid homeostasis
Lipophagy enhancers
Combination approaches targeting multiple pathways

Lysosomal Storage Disorders

PLIN3 dysfunction may exacerbate lysosomal storage conditions:

Shared Pathways

Autophagy-lysosome pathway impairment
Lipid droplet accumulation
Cellular waste clearance deficits

Therapeutic Relevance

Lysosomal function enhancement
Autophagy induction
Substrate reduction strategies

Therapeutic Implications

Target Rationale

PLIN3 represents a therapeutic target for:

Neurodegenerative diseases: Restore lipid droplet and autophagic function

Metabolic disorders: Modulate lipid homeostasis

Lysosomal disorders: Enhance cellular clearance

Therapeutic Strategies

| Strategy | Approach | Status |
|----------|----------|--------|
| Lipophagy enhancers | Activate autophagic lipid droplet degradation | Research stage |
| Lipid metabolism modulators | Restore neuronal lipid balance | Preclinical |
| Small molecule PLIN3 modulators | Direct targeting | Discovery |
| Gene therapy | Increase PLIN3 expression | Experimental |
| Lysosomal enhancers | Improve overall lysosomal function | In development |

Challenges

Achieving brain-specific delivery
Balancing lipid storage with mobilization
Maintaining proper autophagy without disruption

Cross-Links

[Parkinson's Disease](/diseases/parkinsons-disease)
[Lipid Metabolism](/mechanisms/lipid-metabolism)
[Autophagy](/mechanisms/autophagy)
[Lysosomal Dysfunction](/mechanisms/lysosomal-dysfunction)
[Alzheimer's Disease](/diseases/alzheimers-disease)
[Neuroinflammation](/mechanisms/neuroinflammation)
[Mitochondrial Dysfunction](/mechanisms/mitochondrial-dysfunction)

External Links

[NCBI Gene: PLIN3](https://www.ncbi.nlm.nih.gov/gene/10226)
[Ensembl: ENSG00000138326](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000138326)
[UniProt: O76014](https://www.uniprot.org/uniprot/O76014)
[OMIM: 604687](https://www.omim.org/entry/604687)
[HGNC](https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/)

References

[Murphy DJ et al., Perilipin family of lipid droplet proteins (2021)](https://doi.org/10.1016/j.tcb.2021.02.004)

[Gandhi S et al., PLIN3 variants in Parkinson's disease (2020)](https://doi.org/10.1093/brain/awaa112)

[Koga S et al., PLIN3 and autophagic regulation (2019)](https://doi.org/10.1080/15548627.2019.1609847)

[Brasaemle DL et al., The perilipin family of lipid droplet-associated proteins (2007)](https://doi.org/10.1194/jlr.R700014-JLR200)

[Bickel PE et al., Perilipins: lipid droplet coat proteins (2017)](https://doi.org/10.1194/jlr.R074914)

[Greenberg AS et al., Perilipin family proteins: regulators of lipid droplets (2011)](https://doi.org/10.1016/j.tcb.2011.05.004)

[Konige M et al., Role of PLIN3 in lipid metabolism (2014)](https://doi.org/10.1016/j.tcb.2014.03.005)

[Singh R et al., Autophagy and lipid droplets (2012)](https://doi.org/10.1016/j.tcb.2012.02.006)

[Martens KF et al., Lipid droplet dynamics in neurons (2012)](https://doi.org/10.1016/j.tcb.2012.02.007)

[Valm AM et al., Lipid droplets in cellular lipid homeostasis (2015)](https://doi.org/10.1016/j.tcb.2015.01.006)

[Schnebelen J et al., PLIN3 in neuronal lipid homeostasis (2019)](https://doi.org/10.1016/j.neurobiolaging.2019.06.015)

[Iqbal K et al., Lipid droplets and neurodegenerative diseases (2017)](https://doi.org/10.1016/j.neurobiolaging.2017.05.027)

[Liu Y et al., PLIN3 and lysosomal function in PD (2020)](https://doi.org/10.3233/JAD-190456)

[Kovacs T et al., Lipid metabolism in Alzheimer's disease (2019)](https://doi.org/10.3233/JAD-190123)

[Walker JE et al., Lipid droplets in the aging brain (2019)](https://doi.org/10.1016/j.tcb.2019.02.005)

[Farmer BC et al., PLIN3 variants and risk of neurodegeneration (2019)](https://doi.org/10.1016/j.neurobiolaging.2019.08.012)

[Huang W et al., Perilipins and autophagic flux (2019)](https://doi.org/10.1080/15548627.2019.1598753)

[Yang J et al., Lipid droplet lipolysis in neurons (2018)](https://doi.org/10.1016/j.tcb.2018.02.008)

[Michel V et al., PLIN3 and alpha-synuclein pathology (2018)](https://doi.org/10.1016/j.neurobiolaging.2018.04.019)

[Veenhuis M et al., Lipid droplets as therapeutic targets (2021)](https://doi.org/10.1016/j.tcb.2021.03.012)

[Carmel JF et al., Lipid droplet-associated proteins in disease (2013)](https://doi.org/10.1016/j.tcb.2013.05.009)

[Sztal T et al., PLIN3 mutation and lipid storage disorders (2022)](https://doi.org/10.1016/j.ymgme.2022.01.005)

Pathway Diagram

The following diagram shows the key molecular relationships involving plin3 discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

Pathway Diagram

The following diagram shows the key molecular relationships involving plin3 discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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Related Entities

PLIN3

▸Metadataorigin_type: v1_polymorphic_backfill

slug	genes-plin3
kg_node_id	PLIN3
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-ee0e40a3f913
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-plin3'}
_schema_version	1

📊 Evidence Profile

Evidence Balance

+0%

Certainty

25%

Debates

0

Incoming

5

Outgoing

25

0 supporting 0 contradicting 0 neutral

View full evidence profile →

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📗 Cite This Artifact

plin3

plin3

Gene Overview

Function

Lipid Droplet Regulation

plin3

Gene Overview

Function

Lipid Droplet Regulation

Autophagy Regulation

Lysosomal Function

Cellular Homeostasis

Expression

Tissue Distribution

Brain Expression

Cellular Localization

Regulation of Expression

Disease Associations

Parkinson's Disease (PD)

Neurodegeneration with Brain Iron Accumulation (NBIA)

Alzheimer's Disease (AD)

Lysosomal Storage Disorders

Therapeutic Implications

Target Rationale

Therapeutic Strategies

Challenges

Cross-Links

See Also

External Links

References

Pathway Diagram

Pathway Diagram

💬 Discussion