<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">PLIN5 — Perilipin 5</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>PLIN5</td>
</tr>
<tr>
<td class="label">Gene Name</td>
<td>Perilipin 5 (OXPAT)</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>9q34.3</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>440503</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000165030</td>
</tr>
<tr>
<td class="label">OMIM ID</td>
<td>613877</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q0VGN5 (PLIN5_HUMAN)</td>
</tr>
<tr>
<td class="label">Total Exons</td>
<td>7</td>
</tr>
<tr>
<td class="label">Transcript Length</td>
<td>~1,500 bp (coding sequence)</td>
</tr>
<tr>
<td class="label">Protein Length</td>
<td>463 amino acids</td>
</tr>
<tr>
<td class="label">Protein Mass</td>
<td>~50 kDa</td>
</tr>
<tr>
<td class="label">Expression Priority Tissues</td>
<td>Heart, skeletal muscle, brown adipose tissue, brain (neurons, astrocytes, microglia)</td>
</tr>
<tr>
<td class="label">Family</td>
<td>Perilipin family (PLIN1-5)</td>
</tr>
<tr>
<td class="label">Modes of Inheritance</td>
<td>Complex inheritance (metabolic traits); rare monogenic forms</td>
</tr>
<tr>
<td class="label">Tissue</td>
<td>Expression Level</td>
</tr>
<tr>
<td class="label">
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">PLIN5 — Perilipin 5</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>PLIN5</td>
</tr>
<tr>
<td class="label">Gene Name</td>
<td>Perilipin 5 (OXPAT)</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>9q34.3</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>440503</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000165030</td>
</tr>
<tr>
<td class="label">OMIM ID</td>
<td>613877</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q0VGN5 (PLIN5_HUMAN)</td>
</tr>
<tr>
<td class="label">Total Exons</td>
<td>7</td>
</tr>
<tr>
<td class="label">Transcript Length</td>
<td>~1,500 bp (coding sequence)</td>
</tr>
<tr>
<td class="label">Protein Length</td>
<td>463 amino acids</td>
</tr>
<tr>
<td class="label">Protein Mass</td>
<td>~50 kDa</td>
</tr>
<tr>
<td class="label">Expression Priority Tissues</td>
<td>Heart, skeletal muscle, brown adipose tissue, brain (neurons, astrocytes, microglia)</td>
</tr>
<tr>
<td class="label">Family</td>
<td>Perilipin family (PLIN1-5)</td>
</tr>
<tr>
<td class="label">Modes of Inheritance</td>
<td>Complex inheritance (metabolic traits); rare monogenic forms</td>
</tr>
<tr>
<td class="label">Tissue</td>
<td>Expression Level</td>
</tr>
<tr>
<td class="label">Heart (cardiac muscle)</td>
<td>Highest</td>
</tr>
<tr>
<td class="label">Skeletal muscle (type I fibers)</td>
<td>High</td>
</tr>
<tr>
<td class="label">Brown adipose tissue</td>
<td>High</td>
</tr>
<tr>
<td class="label">Slow-twitch muscle</td>
<td>High</td>
</tr>
<tr>
<td class="label">Liver</td>
<td>Low-moderate</td>
</tr>
<tr>
<td class="label">Kidney</td>
<td>Low</td>
</tr>
<tr>
<td class="label">Brain</td>
<td>Moderate (cell-type specific)</td>
</tr>
<tr>
<td class="label">Strategy</td>
<td>Approach</td>
</tr>
<tr>
<td class="label">Small molecule activators</td>
<td>Increase PLIN5 expression/activity</td>
</tr>
<tr>
<td class="label">Gene therapy</td>
<td>AAV-mediated PLIN5 delivery</td>
</tr>
<tr>
<td class="label">Protein therapy</td>
<td>Recombinant PLIN5</td>
</tr>
<tr>
<td class="label">Combination approaches</td>
<td>PLIN5 + metabolic modulators</td>
</tr>
<tr>
<td class="label">Interactor</td>
<td>Function</td>
</tr>
<tr>
<td class="label">ATGL</td>
<td>Adipose triglyceride lipase</td>
</tr>
<tr>
<td class="label">CPT1</td>
<td>Carnitine palmitoyltransferase 1</td>
</tr>
<tr>
<td class="label">Mitochondrial proteins</td>
<td>Fatty acid oxidation enzymes</td>
</tr>
<tr>
<td class="label">PPARα</td>
<td>Nuclear receptor for fatty acids</td>
</tr>
<tr>
<td class="label">PGC-1α</td>
<td>Transcriptional coactivator</td>
</tr>
<tr>
<td class="label">Rab GTPases</td>
<td>Vesicle trafficking</td>
</tr>
<tr>
<td class="label">Perilipin-2</td>
<td>Related lipid droplet protein</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">2 edges</a></td>
</tr>
</table>
PLIN5 (Perilipin 5), also known as OXPAT ( oxidative tissue-enriched PAT protein), encodes a lipid droplet-associated protein that is highly expressed in oxidative tissues including the heart, skeletal muscle, and brown adipose tissue. Perilipin-5 is a member of the perilipin family of proteins that coat the surface of lipid droplets, playing critical roles in regulating lipid storage, fatty acid oxidation, and cellular energy metabolism [@dalen2007][@kimmel2010]. Unlike other perilipin family members that are primarily expressed in adipocytes, PLIN5 is enriched in tissues with high fatty acid oxidation rates, reflecting its specialized function in coordinating lipid storage with mitochondrial fatty acid oxidation.
Beyond its well-characterized role in metabolic tissues, emerging research has revealed that PLIN5 is expressed in the brain, particularly in neurons, astrocytes, and microglia, where it plays increasingly recognized roles in lipid metabolism, oxidative stress, and neurodegenerative disease processes [@wang2015][@liu2020]. Increased PLIN5 expression and lipid droplet accumulation have been documented in Alzheimer's disease, Parkinson's disease, and other neurodegenerative conditions, where they contribute to disease pathogenesis through mechanisms involving lipotoxicity, mitochondrial dysfunction, and neuroinflammation.
Perilipin-5 is a peripheral membrane protein that associates with the surface of lipid droplets through interactions with the phospholipid monolayer. The protein contains several structural features that mediate its unique functions in fatty acid oxidation:
The N-terminal region of PLIN5 contains the PAT domain (named after perilipin, adipocyte differentiation-related protein, and TIP47), which is conserved among all perilipin family members and mediates lipid droplet targeting [@dalen2007]. This domain specifically recognizes lipid droplet surfaces and is essential for the localization of PLIN5 to these organelles.
The central region of PLIN5 contains unique features not found in other perilipin family members:
The C-terminal region of PLIN5 is relatively basic and contains:
PLIN5 undergoes several post-translational modifications:
Like other perilipin family members, PLIN5 coats the surface of lipid droplets, providing a protective layer that regulates access to stored triglycerides [@dalen2007]. However, PLIN5 has distinct functions compared to adipocyte-specific perilipins:
PLIN5 plays a unique role in coordinating lipid storage with fatty acid oxidation [@kimmel2010][@polls2009]:
A key function of PLIN5 is protecting cells against the toxic effects of excess fatty acids [@gravey2016]:
In the heart, PLIN5 is highly expressed and plays essential roles:
In skeletal muscle, PLIN5 regulates:
In the brain, PLIN5 is expressed in multiple cell types with distinct functions:
Neurons: PLIN5 expression in neurons is associated with:
PLIN5 is implicated in various forms of heart disease:
PLIN5 is associated with features of metabolic syndrome:
PLIN5 is significantly implicated in Alzheimer's disease through multiple mechanisms [@liu2020][@yang2021]:
PLIN5 is implicated in Parkinson's disease through:
PLIN5 is implicated in ALS through:
PLIN5 expression is altered in Huntington's disease and may contribute to:
PLIN5 is highly expressed in oxidative tissues:
In these tissues, PLIN5 is localized to lipid droplets and is particularly enriched at contact sites between lipid droplets and mitochondria.
In the brain, PLIN5 expression is cell-type specific:
Neurons: PLIN5 is expressed in various neuronal populations, particularly in:
Microglia: PLIN5 is expressed in activated microglia and is associated with lipid droplet accumulation.
PLIN5 expression is regulated by:
Several therapeutic strategies targeting PLIN5 are being developed:
PLIN5 represents a promising therapeutic target for neurodegenerative diseases:
Plin5−/− mice: Complete knockout of PLIN5 leads to:
Tissue-specific knockouts: Conditional deletion in heart, muscle, or brain reveals tissue-specific functions.
Plin5−/−; 5xFAD mice: Cross with Alzheimer's disease model shows altered amyloid pathology and cognitive function.
Plin5−/−; MPTP mice: Cross with Parkinson's disease model reveals enhanced dopaminergic neuron loss.
PLIN5 participates in several key cellular signaling pathways:
PLIN5 is a target of PPARα, a nuclear receptor that regulates fatty acid metabolism:
PLIN5 modulates lipolysis through:
PLIN5 in glial cells is linked to inflammatory pathways:
PLIN5 interacts with multiple proteins and cellular structures:
2020: Liu et al. demonstrated that PLIN5 plays important roles in neuronal lipid metabolism and neurodegeneration, establishing a link between PLIN5 and AD pathogenesis [@liu2020].
2021: Yang et al. showed that lipid droplet accumulation in neurons drives cognitive decline in Alzheimer's disease, with PLIN5 being a key player in this process [@yang2021].
2022: Chen et al. demonstrated that perilipin-5 regulates mitochondrial function and lipid metabolism in dopaminergic neurons, with implications for Parkinson's disease [@chen2022].
2022: Zhang et al. provided direct evidence that PLIN5 deficiency exacerbates Parkinson's disease pathology through mitochondrial dysfunction, positioning PLIN5 as a protective factor in PD [@zhang2022].
2023: Wang et al. reviewed the therapeutic potential of targeting PLIN5 for neurodegenerative diseases, highlighting both opportunities and challenges [@wang2023].
2023: Liu et al. established lipid droplet accumulation in microglia as a new paradigm in neurodegeneration, with PLIN5 playing a central role in microglial lipid metabolism [@liu2023].
2023: Xu et al. explored the relationship between PLIN5 and oxidative stress in aging and neurodegeneration, highlighting the role of lipid peroxidation and antioxidant responses [@xu2023].
2024: Chen et al. identified genetic variants in PLIN5 that modulate susceptibility to Alzheimer's disease, providing human genetic evidence for a causal role of PLIN5 in AD [@chen2024].
2024: Lin et al. demonstrated a role for perilipin-5 in synaptic function and memory formation, linking lipid metabolism to cognitive processes [@lin2024].
2024: Zhao et al. reviewed the role of PLIN5 in protein aggregation diseases, synthesizing evidence across AD, PD, and ALS contexts [@zhao2024].
The clinical spectrum of PLIN5-related metabolic disease includes:
As the role of PLIN5 in neurodegeneration becomes clearer:
PLIN5 is evolutionarily conserved across species:
PLIN5 (Perilipin 5), also known as OXPAT, is a lipid droplet-associated protein highly expressed in oxidative tissues including heart, skeletal muscle, and brain. PLIN5 regulates lipid storage and coordinates fatty acid oxidation with mitochondrial function, playing critical roles in cellular energy metabolism. Mutations in PLIN5 cause cardiomyopathy and metabolic disorders, while dysregulated PLIN5 expression has been implicated in neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and ALS. PLIN5 contributes to neurodegeneration through lipid droplet accumulation in neurons and glia, mitochondrial dysfunction, oxidative stress, and neuroinflammation. Recent research demonstrating that PLIN5 deficiency exacerbates pathology in Parkinson's disease models positions PLIN5 as a promising therapeutic target. Future research directions include the development of pharmacological modulators of PLIN5 activity suitable for CNS delivery, further characterization of PLIN5's role in specific neurodegenerative disease subtypes, and clinical translation of lipid metabolism-targeted approaches.