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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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PLIN1
perilipin 1
Chromosome 15 · 15q26.1
NCBI Gene: 5346Ensembl: ENSG00000166819.13HGNC: HGNC:9076UniProt: O60240
114PubMed Papers
21Diseases
0Drugs
7Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindinglipid catabolic processlipid dropletlipid bindingPLIN1-related familial partial lipodystrophydiabetic neuropathymonogenic diabetessmall intestine neoplasm
✦AI Summary

PLIN1 (perilipin 1) is a lipid droplet-associated protein that serves as a critical modulator of lipid metabolism in adipocytes and other metabolic tissues. PLIN1 coats the surface of lipid droplets, functioning as a protective barrier that shields stored triglycerides from degradation by hormone-sensitive lipase (HSL) and regulates lipolysis through dynamic protein-protein interactions 1. At the molecular level, PLIN1 contains an amino-terminal PAT domain and an 11-mer repeat region that enables binding to lipid droplet surfaces with high avidity, particularly to droplets fully covered by phospholipids 2. PLIN1 works synergistically with CIDEC to promote unilocular lipid droplet formation and enlargement through directional neutral lipid transfer 3. PLIN1 expression correlates positively with mitochondrial biogenesis genes and increases following weight loss, suggesting metabolic adaptation 3. Clinically, PLIN1 mutations cause familial partial lipodystrophy-4 4, while pathogenic PLIN1 variants are associated with nonalcoholic fatty liver disease (NAFLD) and fibrosis 4. Beyond adipocytes, PLIN1 regulates macrophage polarization and atherosclerotic plaque stability by promoting stable lipid storage and anti-inflammatory phenotypes 5. Additionally, PLIN1 serves as a direct target of the farnesoid X receptor (FXR), stabilizing lipid droplets to prevent hepatic stellate cell activation and liver fibrosis 6. These findings establish PLIN1 as a multifunctional lipid droplet protein with therapeutic relevance in metabolic diseases.

Sources cited
1
PLIN1 domain organization and role in regulating lipase recruitment and lipolysis
PMID: 38140813
2
PLIN1 upregulation controls lipid droplet structure and NAFLD severity; pathogenic PLIN1 frameshift variant associated with familial partial lipodystrophy
PMID: 36029129
3
PLIN1 regulates lipolysis through interaction with ABHD5 and controls hormone-sensitive lipase activity
PMID: 32168372
4
PLIN1 expression decreased in obesity and involved in lipolysis regulation
PMID: 39761791
5
FXR upregulates PLIN1 to stabilize lipid droplets and prevent hepatic stellate cell activation
PMID: 31932588
6
PLIN1 binds to lipid droplets fully covered by phospholipids with high avidity
PMID: 39297796
7
PLIN1 gene expression correlates with mitochondrial genes and increases after weight loss in human adipose tissue
PMID: 24126816
8
PLIN1 regulates macrophage inflammatory polarity and is associated with plaque stability in atherosclerosis
PMID: 35662076
Disease Associationsⓘ21
PLIN1-related familial partial lipodystrophyOpen Targets
0.73Strong
diabetic neuropathyOpen Targets
0.19Weak
monogenic diabetesOpen Targets
0.15Weak
small intestine neoplasmOpen Targets
0.14Weak
gliomaOpen Targets
0.10Suggestive
hepatocellular carcinomaOpen Targets
0.09Suggestive
breast cancerOpen Targets
0.09Suggestive
liposarcomaOpen Targets
0.08Suggestive
polycystic ovary syndromeOpen Targets
0.07Suggestive
type 2 diabetes mellitusOpen Targets
0.07Suggestive
neoplasmOpen Targets
0.07Suggestive
non-alcoholic fatty liver diseaseOpen Targets
0.06Suggestive
CIDEC-related familial partial lipodystrophyOpen Targets
0.06Suggestive
LIPE-related familial partial lipodystrophyOpen Targets
0.05Suggestive
obesity due to melanocortin 4 receptor deficiencyOpen Targets
0.05Suggestive
glioblastoma multiformeOpen Targets
0.05Suggestive
Hyperlipoproteinemia type 1Open Targets
0.05Suggestive
familial partial lipodystrophy, Kobberling typeOpen Targets
0.05Suggestive
Familial partial lipodystrophy, Köbberling typeOpen Targets
0.05Suggestive
lipodystrophyOpen Targets
0.05Suggestive
Lipodystrophy, familial partial, 4UniProt
Pathogenic Variants7
NM_002666.5(PLIN1):c.277C>T (p.Arg93Ter)Likely pathogenic
PLIN1-related familial partial lipodystrophy
★☆☆☆2024→ Residue 93
NM_002666.5(PLIN1):c.203_218del (p.Leu68fs)Likely pathogenic
PLIN1-related familial partial lipodystrophy
★☆☆☆2023→ Residue 68
NM_002666.5(PLIN1):c.1210-1delPathogenic
PLIN1-related familial partial lipodystrophy
★☆☆☆2020
NM_002666.5(PLIN1):c.1308_1309del (p.Pro439fs)Pathogenic
PLIN1-related familial partial lipodystrophy
☆☆☆☆2022→ Residue 439
NM_002666.5(PLIN1):c.1201_1202dup (p.Val402fs)Pathogenic
PLIN1-related familial partial lipodystrophy
☆☆☆☆2022→ Residue 402
NM_002666.5(PLIN1):c.1191_1192del (p.Val398fs)Pathogenic
PLIN1-related familial partial lipodystrophy
☆☆☆☆2011→ Residue 398
NM_002666.5(PLIN1):c.1210-1G>TPathogenic
PLIN1-related familial partial lipodystrophy
☆☆☆☆2011
View on ClinVar ↗
Related Genes
CIDEAProtein interaction100%FABP4Protein interaction100%LIPEProtein interaction100%PRKACAProtein interaction99%PRKACGProtein interaction99%PRKACBProtein interaction99%
Tissue Expression6 tissues
Liver
100%
Heart
32%
Brain
11%
Ovary
10%
Bone Marrow
3%
Lung
3%
Gene Interaction Network
Click a node to explore
PLIN1CIDEAFABP4LIPEPRKACAPRKACGPRKACB
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt O60240
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.20LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.91 [0.70–1.20]
RankingsWhere PLIN1 stands among ~20K protein-coding genes
  • #4,162of 20,598
    Most Researched114 · top quartile
  • #3,178of 5,498
    Most Pathogenic Variants7
  • #12,613of 17,882
    Most Constrained (LOEUF)1.20
Genes detectedPLIN1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Molecular mechanisms of perilipin protein function in lipid droplet metabolism.
PMID: 38140813
FEBS Lett · 2024
1.00
2
RIPK3 dampens mitochondrial bioenergetics and lipid droplet dynamics in metabolic liver disease.
PMID: 36029129
Hepatology · 2023
0.90
3
Adipocyte lipolysis: from molecular mechanisms of regulation to disease and therapeutics.
PMID: 32168372
Biochem J · 2020
0.80
4
Adipose ZFP36 protects against diet-induced obesity and insulin resistance.
PMID: 39761791
Metabolism · 2025
0.70
5
PLIN1 gene: fat keeper and prevention switcher.
PMID: 20075266
J Appl Physiol (1985) · 2010
0.60