Affinage

PLIN2

Perilipin-2 · UniProt Q99541

Length
437 aa
Mass
48.1 kDa
Annotated
2026-04-28
100 papers in source corpus 27 papers cited in narrative 28 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PLIN2 is a constitutively expressed lipid droplet (LD) coat protein that gates access of lipases and autophagic machinery to stored neutral lipids, thereby serving as a central regulator of intracellular lipid homeostasis. PLIN2 directly binds phospholipids (phosphatidylcholine, sphingomyelin) and neutral lipids (cholesterol, stearic acid) on the LD monolayer surface, stabilizing triglyceride and cholesteryl ester stores and preventing both ATGL-mediated cytosolic lipolysis and ATG7-dependent lipophagy (PMID:22744009, PMID:28548876, PMID:33923083). PLIN2 turnover is controlled by at least two degradation axes—MARCH6/TEB4-mediated ubiquitin–proteasome recognition of its N-terminally acetylated residue, and AMPK-phosphorylation-dependent chaperone-mediated autophagy via Hsc70—and removal of PLIN2 is a prerequisite for lipid mobilization (PMID:30425097, PMID:26902588, PMID:35614132). On the LD surface PLIN2 recruits Rab18 and ACSL3 into a complex that promotes LD biogenesis, sequesters the SNARE protein SNAP23 to modulate insulin-stimulated glucose uptake, and in Drosophila cooperates with retinol dehydrogenase to limit Bmm/ATGL access, illustrating conserved scaffold and gatekeeper functions across species (PMID:33713834, PMID:24040030, PMID:35132760).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1999 Medium

    Establishing that PLIN2 actively participates in fatty acid uptake resolved an early question about whether PLIN2 is merely a passive LD marker or has a functional role in lipid handling.

    Evidence Transfection of COS-7 cells with ADRP cDNA followed by kinetic fatty acid uptake assays

    PMID:10358026

    Open questions at the time
    • Mechanism of fatty acid uptake facilitation (channel, flipase, or indirect) was not defined
    • No loss-of-function confirmation
  2. 2002 High

    Demonstrating that PLIN2 localizes to LD surfaces and that it belongs to the conserved PAT family with perilipin and TIP47 established the conceptual framework of a shared LD-coat protein family governing lipid deposition and mobilization.

    Evidence GFP-tagged protein localization; cross-species heterologous expression in mammalian, Drosophila, and Dictyostelium systems; adenoviral overexpression in fibroblasts

    PMID:12077142 PMID:12217895

    Open questions at the time
    • Structural basis of LD targeting was not resolved
    • Functional redundancy among PAT family members was not dissected
  3. 2005 Medium

    Identifying PLIN2 as a substrate of the ubiquitin–proteasome pathway showed that LD regression requires active protein degradation, linking PLIN2 turnover to triglyceride mobilization.

    Evidence MG-132 proteasome inhibition; detection of polyubiquitinated ADRP; lipid quantification in macrophages and hepatoma cells

    PMID:15336557 PMID:16230742

    Open questions at the time
    • The responsible E3 ligase was not identified at this stage
    • Whether proteasomal degradation was sufficient or merely permissive for lipolysis was unclear
  4. 2006 High

    Genetic ablation of PLIN2 combined with Tip47 knockdown revealed functional compensation between PAT family members and showed that loss of both redirects fatty acids from triglycerides to phospholipids, establishing PLIN2's role in neutral lipid partitioning.

    Evidence ADFP-null cell lines; Tip47 siRNA double knockdown; NEFA uptake and lipolysis assays; mass spectrometry

    PMID:16532261 PMID:16968708

    Open questions at the time
    • Relative quantitative contributions of PLIN2 vs. Tip47 in different tissues were unknown
    • Whether CGI-58 interaction with PLIN2 has a functional consequence distinct from its perilipin interaction was not tested
  5. 2012 High

    Live-cell FRET demonstrated that PLIN2 directly contacts phospholipids and cholesterol at molecular distances on LD surfaces, transforming the model from co-fractionation-based association to a direct lipid-binding protein.

    Evidence CFP-Plin2 FRET with fluorescently labeled lipids; pixel-by-pixel efficiency mapping; lipid profiling in overexpressing cells

    PMID:20473576 PMID:22744009

    Open questions at the time
    • Binding domains/residues mediating individual lipid interactions were not mapped
    • No structural model of PLIN2-lipid interface existed
  6. 2013 High

    Identification of the Ser251Pro variant that alters LD number, lipolysis rate, and plasma triglycerides in humans connected PLIN2 structure to human lipid metabolism, while FRET-based discovery of PLIN2-SNAP23 interaction linked LD biology to GLUT4 vesicle trafficking and glucose uptake.

    Evidence HEK293 stable transfection with S251P; population genotyping (n=2113); live-cell FRET and co-IP of PLIN2–SNAP23; glucose uptake assays with KD and OE

    PMID:23603836 PMID:24040030

    Open questions at the time
    • Causal relationship of S251P to plasma TG in Mendelian framework was not established
    • How SNAP23 sequestration on LDs impairs GLUT4 exocytosis mechanistically was not fully resolved
  7. 2016 High

    Discovery that AMPK phosphorylates PLIN2 after Hsc70 binding to prime it for chaperone-mediated autophagy (CMA) identified the kinase and chaperone that initiate LD mobilization, establishing CMA as the first degradation route for LD-associated PLIN2.

    Evidence AMPK inhibitor/activator treatments; co-IP of PLIN2 with Hsc70; phosphorylation and CMA degradation assays

    PMID:26902588

    Open questions at the time
    • Specific phosphorylation sites were not mapped
    • Relative contribution of CMA vs. proteasomal degradation in different tissues was undefined
  8. 2017 High

    Genetic epistasis in mice and Drosophila placed PLIN2 as a guardian against ATG7-dependent macroautophagy of LDs (lipophagy), while an HDAC6-Hsc70-PLIN2 axis in Drosophila confirmed conserved chaperone-dependent PLIN2 turnover controls fat storage across species.

    Evidence plin2−/− mice; atg7−/− MEFs double-mutant epistasis; Drosophila HDAC6 mutants with PLIN2 reduction rescue; lipid phenotyping

    PMID:28102311 PMID:28548876 PMID:28966044

    Open questions at the time
    • Whether PLIN2 physically occludes autophagosome receptors on the LD surface or acts indirectly was not determined
    • Identity of the autophagy receptor recognizing PLIN2-depleted LDs remained unknown
  9. 2018 High

    Identification of MARCH6/TEB4 as the E3 ubiquitin ligase targeting PLIN2's N-terminal acetyl group via the Ac/N-end rule pathway resolved the long-sought ubiquitin ligase identity and provided a molecular mechanism for proteasomal PLIN2 degradation.

    Evidence Cycloheximide chase; in vivo ubiquitylation assays; split-ubiquitin yeast two-hybrid; chemical cross-linking co-IP in HeLa/HEK293T/HepG2 cells

    PMID:30425097

    Open questions at the time
    • Whether MARCH6-mediated degradation occurs on or off the LD surface was not determined
    • Additional E3 ligases may target PLIN2 under different conditions
  10. 2021 High

    Characterization of a PLIN2-Rab18-ACSL3 complex on LDs and the demonstration that liver-specific PLIN2 loss activates converging ATGL-lipolysis and lipophagy pathways revealed PLIN2 as both a scaffold for LD biogenesis machinery and a dual gatekeeper against two independent lipid mobilization routes.

    Evidence Co-IP and subcellular fractionation in C2C12 cells; liver-specific PLIN2 KO mice with pharmacological inhibition of ATGL and autophagy; fatty acid oxidation assays; adrenal Plin2−/− CE/cholesterol phenotyping

    PMID:33582145 PMID:33713834 PMID:33923083

    Open questions at the time
    • Structural details of the PLIN2-Rab18 interface were not resolved
    • How the two lipid mobilization pathways are coordinated temporally remained unclear
  11. 2022 High

    Studies in ESCs and Drosophila extended PLIN2's gatekeeper role to developmental biology: CMA-mediated PLIN2 degradation upon exit from pluripotency drives LD mobilization that supplies acetyl-CoA for histone acetylation, while a Drosophila RDH-Plin2 axis limits ATGL access to LDs, demonstrating that PLIN2 controls epigenetic reprogramming and conserved lipolytic regulation.

    Evidence Plin2 KO ESCs with lipidomics, mitochondrial imaging, ChIP for histone acetylation; Drosophila RNAi screen with genetic epistasis and LD size quantification

    PMID:35132760 PMID:35614132

    Open questions at the time
    • Which specific histone marks and genomic loci are most sensitive to PLIN2-dependent acetyl-CoA flux was not comprehensively mapped
    • Whether the RDH-Plin2 axis operates in mammalian cells is untested
  12. 2024 Medium

    Discovery that TRIB3 physically shields PLIN2 from MARCH6/TEB4-mediated ubiquitination in renal cell carcinoma identified a disease-relevant stabilizer of PLIN2, expanding the regulatory network controlling its abundance.

    Evidence Co-IP; TRIB3 knockdown; ubiquitination assays; PLIN2 stability measurements in RCC cells

    PMID:38561354

    Open questions at the time
    • Whether TRIB3-PLIN2 interaction occurs on the LD surface or in the cytosol is unknown
    • Generalizability of TRIB3 stabilization beyond RCC was not tested
    • Single lab, awaits independent confirmation

Open questions

Synthesis pass · forward-looking unresolved questions
  • A high-resolution structural model of PLIN2 bound to the LD phospholipid monolayer remains unavailable, leaving unresolved how PLIN2 simultaneously engages lipids, Rab18, SNAP23, and degradation machinery, and how tissue-specific regulatory hierarchies (CMA vs. MARCH6 vs. lipophagy) are coordinated.
  • No atomic-resolution structure of full-length PLIN2 or its lipid-bound form
  • Tissue-specific hierarchy of CMA, proteasomal, and lipophagy-based PLIN2 removal is undefined
  • How PLIN2 loss permits autophagosome recruitment at a molecular level (receptor identity) is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 4 GO:0008289 lipid binding 2
Localization
GO:0005811 lipid droplet 4 GO:0005829 cytosol 2
Pathway
R-HSA-1430728 Metabolism 5 R-HSA-9612973 Autophagy 4 R-HSA-392499 Metabolism of proteins 3
Partners
ABHD5ACSL3ARF1HSPA8MARCH6RAB18SNAP23TRIB3
Complex memberships
PLIN2-Rab18-ACSL3 complex

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 PLIN2 (ADRP) facilitates long-chain fatty acid uptake in transfected COS-7 cells, increasing the initial rate of oleic acid, palmitate, and arachidonate uptake but not medium-chain fatty acids or glucose, acting as a saturable transport component. Transfection of COS-7 cells with ADRP cDNA followed by fatty acid uptake assays (dose-response, temperature dependence, kinetic analysis) The Journal of biological chemistry Medium 10358026
2002 PLIN2 (ADRP) overexpression in murine fibroblasts stimulates lipid droplet formation and triacylglycerol accumulation, with GFP-ADRP localizing to the surface of lipid droplets in a ring-shaped pattern, independent of adipocyte-specific gene induction. Adenoviral GFP-ADRP overexpression in murine fibroblasts; confocal microscopy; triacylglycerol content measurement American journal of physiology. Endocrinology and metabolism Medium 12217895
2002 PLIN2 (ADRP), along with Perilipin and TIP47, belongs to a conserved PAT protein family whose sequence/structural elements are necessary and sufficient to direct association to lipid droplet surfaces across species (mammals, Drosophila, Dictyostelium), indicating a common function in lipid deposition and/or mobilization. GFP-tagged protein co-localization with isolated lipid droplets; immunofluorescence; cross-species heterologous expression The Journal of biological chemistry High 12077142
2005 PLIN2 (ADRP) protein is degraded via the ubiquitin-proteasome pathway during regression of lipid-storing cells; proteasome inhibition blocks ADRP decrease and accumulates polyubiquitinated ADRP, and ADRP degradation and triglyceride reduction are co-regulated. Proteasome inhibitor treatment (MG-132); immunoblotting for polyubiquitinated ADRP; lipid quantification in J774 macrophages and HuH-7 cells Journal of lipid research Medium 16230742
2004 ARF1 (GDP-bound form) interacts with a central domain of PLIN2 (ADRP) and induces its dissociation from lipid droplet surfaces; brefeldin A or dominant-negative ARF1 causes ADRP dissociation from lipid droplets. Yeast two-hybrid screening; GST pull-down; co-immunoprecipitation; brefeldin A treatment; dominant-negative ARF1 overexpression; deletion mutant analysis Biochemical and biophysical research communications High 15336557
2006 CGI-58 (causal gene of Chanarin-Dorfman syndrome) was identified as an interaction partner of both PLIN2 (ADRP) and perilipin via yeast two-hybrid screening; CGI-58 co-localizes with perilipin at lipid droplet surfaces in 3T3-L1 cells and specific interaction with perilipin was confirmed by GST pull-down. Yeast two-hybrid screening; GST pull-down; fluorescence microscopy co-localization Molecular and cellular biochemistry Medium 16532261
2006 In PLIN2 (ADFP) null embryonic cells, Tip47 compensates as the sole lipid droplet-associated PAT protein; double knockdown of ADFP and Tip47 impairs lipid droplet formation and redirects exogenous NEFA from triglycerides to phospholipids, demonstrating that PLIN2 and Tip47 regulate lipid droplet formation and neutral lipid partitioning. ADFP null cell lines; Tip47 siRNA knockdown; mass spectrometry identification; immunoblot; immunocytochemistry; NEFA uptake and lipolysis assays The Journal of biological chemistry High 16968708
2010 PLIN2 (ADRP) binds sphingomyelin and phosphatidylcholine with high affinity (nanomolar range) in fluorescence binding assays, identifying PLIN2 as a phospholipid-binding protein at lipid droplet surfaces. Fluorescence binding assays with NBD-labeled lipids; fractionation of lipid droplet proteins Lipids Medium 20473576
2012 PLIN2 directly interacts with phosphatidylcholine, sphingomyelin, stearic acid, and cholesterol on lipid droplet surfaces in live cells, at molecular distances of 44–57 Å; Plin2 overexpression upregulates enzymes for triacylglycerol, cholesteryl ester, and phospholipid synthesis while decreasing lipolytic enzyme expression. Live-cell FRET between CFP-Plin2 and fluorescently labeled lipids; pixel-by-pixel FRET efficiency mapping; lipid content analysis in overexpressing cells American journal of physiology. Cell physiology High 22744009
2013 PLIN2 Ser251Pro missense variant disrupts a predicted α-helix in the protein, leading to increased lipid accumulation, decreased lipolysis, and increased number of small lipid droplets per cell in HEK293 cells; the Pro251 allele is associated with reduced plasma triglyceride and VLDL concentrations in humans. 3D structure modeling; stable transfection of HEK293 cells; lipid droplet size distribution analysis; lipolysis assays; human population genotyping (n=2113) FASEB journal High 23603836
2013 PLIN2 interacts with SNAP23 (a SNARE protein) on lipid droplets within 51 Å (measured by FRET), and PLIN2 overexpression increases SNAP23 partitioning to lipid droplets and decreases insulin-mediated glucose uptake, while PLIN2 knockdown increases glucose uptake. Live-cell FRET; co-immunoprecipitation; co-localization microscopy; 2-NBD-glucose and [3H]-2-deoxyglucose uptake assays; RNAi knockdown in L cells and 3T3-L1 cells PloS one High 24040030
2016 PLIN2 phosphorylation is dependent on AMPK and occurs after PLIN2 interacts with the CMA chaperone HSPA8/Hsc70; this phosphorylation primes PLIN2 for chaperone-mediated autophagy (CMA)-dependent degradation, which is required to initiate lipolysis. AMPK inhibitor/activator treatments; co-immunoprecipitation of PLIN2 with Hsc70; phosphorylation assays; CMA degradation assays Autophagy High 26902588
2017 PLIN2 overexpression protects lipid droplets against macroautophagy, whereas PLIN2 deficiency enhances autophagy and depletes hepatic triglycerides; in atg7-/- MEFs devoid of autophagy, PLIN2 deficiency no longer reduces cellular TG, demonstrating that PLIN2 guards lipid droplets against autophagic degradation via an ATG7-dependent pathway. plin2-/- mice; adenovirus-shAtg7 hepatic knockdown; atg7-/- MEFs; TG quantification; autophagy assays Autophagy High 28548876
2018 TEB4 (MARCH6), an E3 ubiquitin ligase of the Ac/N-end rule pathway, directly targets the N-terminal acetyl moiety of Nα-terminally acetylated PLIN2 for polyubiquitylation and proteasomal degradation; this pathway reduces intracellular lipid droplet accumulation by degrading unbound PLIN2. Cycloheximide chase; in vivo ubiquitylation assays; split-ubiquitin yeast two-hybrid; chemical cross-linking-based reciprocal co-immunoprecipitation; HeLa, HEK293T, HepG2 cell lines The Journal of biological chemistry High 30425097
2021 Rab18 is translocated from the ER to lipid droplets during oleic acid-induced LD accumulation and binds the C terminus of PLIN2; LD localization of Rab18 is diminished when PLIN2 is depleted; LD-associated Rab18 further interacts with ACSL3, forming a PLIN2-Rab18-ACSL3 complex that regulates LD accumulation in myoblasts. Co-immunoprecipitation; PLIN2 depletion; Rab18 overexpression and loss-of-function; subcellular fractionation; triacylglycerol assays in C2C12 cells Biochimica et biophysica acta. Molecular and cell biology of lipids Medium 33713834
2021 SARS-CoV-2 nucleocapsid protein drives DGAT1/2 gene expression to facilitate lipid droplet formation and associates with ADRP (PLIN2) on the LD surface to complete the viral replication cycle; ADRP is essential for SARS-CoV-2 replication. Gene depletion (DGAT, ADRP); viral protein synthesis assays; co-localization of nucleocapsid with ADRP on LDs; hamster in vivo model Cell discovery Medium 34702802
2021 In liver-specific PLIN2 knockout mice, protection against NAFLD results from the integrated actions of both ATGL-mediated lipolysis and lipophagy; inhibition of either ATGL or autophagy blunted increased fatty acid oxidation in PLIN2-deficient hepatocytes, and combined inhibition had no additive effect, indicating these pathways converge. Liver-specific PLIN2 KO mice; ex vivo p62 flux assays; ATGL inhibitor; autophagy inhibitor; fatty acid oxidation assays in primary hepatocytes Cells High 33923083
2022 PLIN2 is required for multipolar spindle formation in hepatocellular carcinoma cells with Trip13 depletion; lipid droplets act as acentriolar microtubule organizing centers and Plin2-coated LDs participate in aberrant mitotic spindle polarity, induction of DNA damage, and mitotic cell death. Trip13 depletion in HCC cells; Plin2 knockdown; spindle polarity imaging; DNA damage assays; lipid droplet characterization Advanced science Medium 36031387
2022 Upon exit from pluripotency, Plin2 is recognized by Hsc70 and degraded via chaperone-mediated autophagy to facilitate lipid droplet mobilization; excessive lipid hydrolysis from Plin2 knockout induces lipidomic remodeling (decreased cardiolipin and phosphatidylethanolamine), mitochondrial cristae defects, reduced acetyl-CoA, and decreased histone acetylation. Plin2 knockout ESCs; ATGL inhibition rescue; CMA inhibition; lipidomics; mitochondrial imaging; histone acetylation assays; ChIP Cell death and differentiation High 35614132
2023 CRISPR-Cas9 loss-of-function screens identified MARCH6 (TEB4) E3 ligase as a regulator of PLIN2 post-translational stability and triacylglycerol biosynthesis, thereby influencing LD abundance; screens also identified ubiquitination, transcription, and mitochondrial function genes as PLIN2 regulators. Genome-edited PLIN2 reporter cell lines; parallel CRISPR-Cas9 loss-of-function screens; functional validation of MARCH6 role in TAG biosynthesis and LD abundance Developmental cell High 37494933
2019 Plin2 deficiency in the heart reduces lipophagy, leading to paradoxical increased triglyceride accumulation in cardiomyocytes; after myocardial infarction, Plin2-/- mice have reduced stroke volume and cardiac output, demonstrating that Plin2 is required for proper lipid droplet hydrolysis via lipophagy in the myocardium. Plin2-/- mice; myocardial infarction model; triglyceride quantification; lipophagy assays; cardiac function measurement Scientific reports High 31061399
2021 Plin2 deletion in adrenal cortex increases cholesteryl ester-rich lipid droplet content, elevates unesterified cholesterol, and disrupts cholesterol balance, including ceroid-like multilamellar body accumulation with age; Plin2 thus regulates CE-rich LD metabolism and cellular cholesterol homeostasis in steroidogenic cells. Plin2-/- mice; histological and molecular characterization of adrenal glands; lipid analysis; ACTH/starvation stimulation; lipidomics Journal of lipid research High 33582145
2022 In Drosophila, Plin2 interacts with retinol dehydrogenase (RDH/CG2064) and this RDH-Plin2 axis reduces the overall level and lipid droplet localization of Bmm/ATGL lipase, antagonizing lipolysis and modulating lipid droplet size. RNAi screen in Drosophila; genetic epistasis; protein interaction studies; lipid droplet size quantification EMBO reports Medium 35132760
2017 In Drosophila, HDAC6 physically associates with the chaperone dHsc4/Hsc70 to maintain proteostasis of PLIN2; loss of HDAC6 causes age-dependent ectopic fat accumulation that is ameliorated by reduction of PLIN2, placing HDAC6-Hsc70 upstream of PLIN2 degradation in lipid homeostasis. Drosophila HDAC6 mutants; PLIN2 reduction epistasis; physical association assays; lipid phenotyping Developmental cell High 28966044
2018 Hypoxia markedly stimulates PLIN2 mRNA synthesis and protein expression in human trophoblasts, and PLIN2 (but not PLIN3) knockdown enhances trophoblast apoptotic death while PLIN2 overexpression promotes cell viability, demonstrating a specific role for PLIN2 in protecting trophoblasts against hypoxia-induced apoptosis. Primary human trophoblasts; hypoxia treatment; PLIN2/PLIN3 siRNA knockdown; PLIN2 overexpression; apoptosis assays Endocrinology High 30351430
2017 PLIN2 downregulation in pancreatic β cells is associated with enhanced autophagic flux and accelerated ER stress resolution; PLIN2 genetic ablation in Akita mice mitigates ER stress, reduces β cell apoptosis, and partially restores β cell mass, while PLIN2 overexpression exacerbates fatty acid- and chemical-induced ER stress. plin2-/- Akita mice; PLIN2 KD and OE in β cell lines; autophagic flux assays; ER stress markers; apoptosis assays Scientific reports High 28102311
2024 TRIB3 interacts with PLIN2 to abrogate TEB4-mediated PLIN2 ubiquitination and degradation, thereby maintaining higher PLIN2 levels and facilitating lipid accumulation and ER homeostasis in renal cell carcinoma. Co-immunoprecipitation; TRIB3 knockdown; ubiquitination assays; PLIN2 stability measurements in RCC cells Cell death & disease Medium 38561354
2022 In Drosophila, knocking down subunits of COP9 signalosome (CSN) leads to enlarged lipid droplets by preventing proteasomal degradation of retinol dehydrogenase (RDH/CG2064); RDH interacts with Plin2 and the RDH-Plin2 axis reduces Bmm/ATGL lipase localization on LDs. Drosophila RNAi screen; CSN subunit knockdown; proteasome pathway analysis; protein interaction assays EMBO reports Medium 35132760

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Functional conservation for lipid storage droplet association among Perilipin, ADRP, and TIP47 (PAT)-related proteins in mammals, Drosophila, and Dictyostelium. The Journal of biological chemistry 325 12077142
2002 ADRP stimulates lipid accumulation and lipid droplet formation in murine fibroblasts. American journal of physiology. Endocrinology and metabolism 234 12217895
2016 AMPK-dependent phosphorylation of lipid droplet protein PLIN2 triggers its degradation by CMA. Autophagy 219 26902588
2017 The constitutive lipid droplet protein PLIN2 regulates autophagy in liver. Autophagy 199 28548876
1999 Adipose differentiation related protein (ADRP) expressed in transfected COS-7 cells selectively stimulates long chain fatty acid uptake. The Journal of biological chemistry 188 10358026
1989 Autosomal dominant retinitis pigmentosa (ADRP): localization of an ADRP gene to the long arm of chromosome 3. Genomics 176 2613244
2005 Up-regulation of ADRP in fatty liver in human and liver steatosis in mice fed with high fat diet. Biochemical and biophysical research communications 145 16403437
2003 Drosophila Perilipin/ADRP homologue Lsd2 regulates lipid metabolism. Mechanisms of development 123 14550535
2005 ADRP/adipophilin is degraded through the proteasome-dependent pathway during regression of lipid-storing cells. Journal of lipid research 119 16230742
2006 Functional compensation for adipose differentiation-related protein (ADFP) by Tip47 in an ADFP null embryonic cell line. The Journal of biological chemistry 100 16968708
2008 Inhibition of ADRP prevents diet-induced insulin resistance. American journal of physiology. Gastrointestinal and liver physiology 98 18669627
2000 Stimulation of adipose differentiation related protein (ADRP) expression in adipocyte precursors by long-chain fatty acids. Journal of cellular physiology 92 10623894
2016 Modeling Nonalcoholic Fatty Liver Disease with Human Pluripotent Stem Cell-Derived Immature Hepatocyte-Like Cells Reveals Activation of PLIN2 and Confirms Regulatory Functions of Peroxisome Proliferator-Activated Receptor Alpha. Stem cells and development 84 27308945
2010 Downregulation of hepatic stellate cell activation by retinol and palmitate mediated by adipose differentiation-related protein (ADRP). Journal of cellular physiology 77 20143336
2018 N-terminal acetylation and the N-end rule pathway control degradation of the lipid droplet protein PLIN2. The Journal of biological chemistry 74 30425097
2005 Molecular genetics of autosomal dominant retinitis pigmentosa (ADRP): a comprehensive study of 43 Italian families. Journal of medical genetics 72 15994872
2015 PPARG modulated lipid accumulation in dairy GMEC via regulation of ADRP gene. Journal of cellular biochemistry 70 25169669
2013 Increased Plin2 expression in human skeletal muscle is associated with sarcopenia and muscle weakness. PloS one 66 23977392
2011 Identification of disease-causing mutations in autosomal dominant retinitis pigmentosa (adRP) using next-generation DNA sequencing. Investigative ophthalmology & visual science 65 20861475
2012 Direct interaction of Plin2 with lipids on the surface of lipid droplets: a live cell FRET analysis. American journal of physiology. Cell physiology 64 22744009
2017 PLIN2 is a Key Regulator of the Unfolded Protein Response and Endoplasmic Reticulum Stress Resolution in Pancreatic β Cells. Scientific reports 61 28102311
2006 A large deletion in the adRP gene PRPF31: evidence that haploinsufficiency is the cause of disease. Molecular vision 59 16636657
2023 Parallel CRISPR-Cas9 screens identify mechanisms of PLIN2 and lipid droplet regulation. Developmental cell 55 37494933
2022 Plin2-mediated lipid droplet mobilization accelerates exit from pluripotency by lipidomic remodeling and histone acetylation. Cell death and differentiation 54 35614132
2019 Plin2-deficiency reduces lipophagy and results in increased lipid accumulation in the heart. Scientific reports 54 31061399
2008 Expression of adipose differentiation-related protein (ADRP) and perilipin in macrophages infected with Mycobacterium leprae. FEMS microbiology letters 53 19054096
2018 PLIN2 Is Essential for Trophoblastic Lipid Droplet Accumulation and Cell Survival During Hypoxia. Endocrinology 52 30351430
2017 Palmitate mediated diacylglycerol accumulation causes endoplasmic reticulum stress, Plin2 degradation, and cell death in H9C2 cardiomyoblasts. Experimental cell research 51 28336294
2013 PLIN2, the major perilipin regulated during sebocyte differentiation, controls sebaceous lipid accumulation in vitro and sebaceous gland size in vivo. Biochimica et biophysica acta 50 23688400
2008 Crystal structures of two coronavirus ADP-ribose-1''-monophosphatases and their complexes with ADP-Ribose: a systematic structural analysis of the viral ADRP domain. Journal of virology 48 18987156
2021 SARS-CoV-2 exploits host DGAT and ADRP for efficient replication. Cell discovery 47 34702802
2013 The minor allele of the missense polymorphism Ser251Pro in perilipin 2 (PLIN2) disrupts an α-helix, affects lipolysis, and is associated with reduced plasma triglyceride concentration in humans. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 46 23603836
2021 Rab18 binds PLIN2 and ACSL3 to mediate lipid droplet dynamics. Biochimica et biophysica acta. Molecular and cell biology of lipids 43 33713834
2006 Regulation of ADRP expression by long-chain polyunsaturated fatty acids in BeWo cells, a human placental choriocarcinoma cell line. Journal of lipid research 42 16391323
2006 Analysis of interaction partners for perilipin and ADRP on lipid droplets. Molecular and cellular biochemistry 40 16532261
2000 RP1 protein truncating mutations predominate at the RP1 adRP locus. Investigative ophthalmology & visual science 40 11095597
2015 PLIN2 inhibits insulin-induced glucose uptake in myoblasts through the activation of the NLRP3 inflammasome. International journal of molecular medicine 38 26166692
2009 ADRP/ADFP and Mal1 expression are increased in macrophages treated with TLR agonists. Atherosclerosis 38 19748622
2006 Regulation of Triglyceride Metabolism. III. Emerging role of lipid droplet protein ADFP in health and disease. American journal of physiology. Gastrointestinal and liver physiology 38 17194897
2004 ADRP is dissociated from lipid droplets by ARF1-dependent mechanism. Biochemical and biophysical research communications 37 15336557
2014 Gene augmentation for adRP mutations in RHO. Cold Spring Harbor perspectives in medicine 36 25037104
2017 Induction of neuroendocrine differentiation in castration resistant prostate cancer cells by adipocyte differentiation-related protein (ADRP) delivered by exosomes. Cancer letters 35 28109910
2015 Genotype and Phenotype Studies in Autosomal Dominant Retinitis Pigmentosa (adRP) of the French Canadian Founder Population. Investigative ophthalmology & visual science 35 26720483
2014 Activation of farnesoid X receptor (FXR) protects against fructose-induced liver steatosis via inflammatory inhibition and ADRP reduction. Biochemical and biophysical research communications 35 24875360
2009 Oleic acid-induced ADRP expression requires both AP-1 and PPAR response elements, and is reduced by Pycnogenol through mRNA degradation in NMuLi liver cells. American journal of physiology. Endocrinology and metabolism 34 19383873
2021 Integrated Action of Autophagy and Adipose Tissue Triglyceride Lipase Ameliorates Diet-Induced Hepatic Steatosis in Liver-Specific PLIN2 Knockout Mice. Cells 32 33923083
2017 HDAC6 Suppresses Age-Dependent Ectopic Fat Accumulation by Maintaining the Proteostasis of PLIN2 in Drosophila. Developmental cell 32 28966044
2013 Expression of PLIN2 and PLIN3 during oocyte maturation and early embryo development in cattle. Theriogenology 32 24210669
2010 Intracellular lipid droplets contain dynamic pools of sphingomyelin: ADRP binds phospholipids with high affinity. Lipids 32 20473576
2019 Targeting PLIN2/PLIN5-PPARγ: Sulforaphane Disturbs the Maturation of Lipid Droplets. Molecular nutrition & food research 30 31325205
2020 UVA Induced Oxidative Stress Was Inhibited by Paeoniflorin/Nrf2 Signaling or PLIN2. Frontiers in pharmacology 29 32499710
2014 Application of next-generation sequencing to identify genes and mutations causing autosomal dominant retinitis pigmentosa (adRP). Advances in experimental medicine and biology 29 24664689
2024 Exercise ameliorates lipid droplet metabolism disorder by the PLIN2-LIPA axis-mediated lipophagy in mouse model of non-alcoholic fatty liver disease. Biochimica et biophysica acta. Molecular basis of disease 28 38306800
2021 Plin2 deletion increases cholesteryl ester lipid droplet content and disturbs cholesterol balance in adrenal cortex. Journal of lipid research 28 33582145
2013 Plin2 inhibits cellular glucose uptake through interactions with SNAP23, a SNARE complex protein. PloS one 28 24040030
2011 Subcellular localization of skeletal muscle lipid droplets and PLIN family proteins OXPAT and ADRP at rest and following contraction in rat soleus muscle. American journal of physiology. Regulatory, integrative and comparative physiology 28 22012700
1992 Point mutations of rhodopsin gene found in Japanese families with autosomal dominant retinitis pigmentosa (ADRP). The Japanese journal of human genetics 27 1391967
2022 Trip13 Depletion in Liver Cancer Induces a Lipogenic Response Contributing to Plin2-Dependent Mitotic Cell Death. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 26 36031387
2005 Expression of adipose differentiation-related protein (ADRP) is conjointly regulated by PU.1 and AP-1 in macrophages. Journal of biochemistry 26 16272134
1998 Stimulation of adipose differentiation related protein (ADRP) expression by ibuprofen and indomethacin in adipocyte precursors and in adipocytes. The Biochemical journal 26 9480894
1993 Structure of the gene encoding mouse adipose differentiation-related protein (ADRP). Genomics 26 8325636
2019 Subclinical atherosclerosis and its progression are modulated by PLIN2 through a feed-forward loop between LXR and autophagy. Journal of internal medicine 24 31251843
2012 Perilipin 2 (PLIN2)-deficiency does not increase cholesterol-induced toxicity in macrophages. PloS one 24 22427949
2010 New SNP of the porcine perilipin 2 (PLIN2) gene, association with carcass traits and expression analysis in skeletal muscle. Molecular biology reports 24 20842447
2012 Transient scrotal hyperthermia induces lipid droplet accumulation and reveals a different ADFP expression pattern between the testes and liver in mice. PloS one 23 23056214
2016 Study on quantitative expression of PPARγ and ADRP in muscle and its association with intramuscular fat deposition of pig. SpringerPlus 21 27652074
2002 [Genetic and molecular characterization of 148 patients with autosomal dominant retinitis pigmentosa (ADRP)]. Archivos de la Sociedad Espanola de Oftalmologia 21 12221539
2024 TRIB3 promotes the progression of renal cell carcinoma by upregulating the lipid droplet-associated protein PLIN2. Cell death & disease 19 38561354
2022 PLIN2 promotes HCC cells proliferation by inhibiting the degradation of HIF1α. Experimental cell research 19 35697078
2006 A study of the nuclear trafficking of the splicing factor protein PRPF31 linked to autosomal dominant retinitis pigmentosa (ADRP). Biochimica et biophysica acta 19 16427773
2025 PLIN2 Promotes Lipid Accumulation in Ascites-Associated Macrophages and Ovarian Cancer Progression by HIF1α/SPP1 Signaling. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 18 39921309
2023 Altered hepatic lipid droplet morphology and lipid metabolism in fasted Plin2-null mice. Journal of lipid research 18 37844775
2015 The perilipin 2 (PLIN2) gene Ser251Pro missense mutation is associated with reduced insulin secretion and increased insulin sensitivity in Italian obese subjects. Diabetes/metabolism research and reviews 18 26443937
2018 The Expression Pattern of PLIN2 in Differentiated Adipocytes from Qinchuan Cattle Analysis of Its Protein Structure and Interaction with CGI-58. International journal of molecular sciences 17 29723991
2017 CEBPA-mediated upregulation of the lncRNA PLIN2 promotes the development of chronic myelogenous leukemia via the GSK3 and Wnt/β-catenin signaling pathways. American journal of cancer research 17 28560057
2020 Lipid droplets are both highly oxidized and Plin2-covered in hepatocytes of diet-induced obese mice. Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme 16 32585124
2020 ADFP promotes cell proliferation in lung adenocarcinoma via Akt phosphorylation. Journal of cellular and molecular medicine 16 33249703
2018 Long-chain metabolites of vitamin E: Interference with lipotoxicity via lipid droplet associated protein PLIN2. Biochimica et biophysica acta. Molecular and cell biology of lipids 16 29733984
2018 The ADRP domain from a virulent strain of infectious bronchitis virus is not sufficient to confer a pathogenic phenotype to the attenuated Beaudette strain. The Journal of general virology 16 29893665
2018 A novel mutation in the PRPF31 in a North Indian adRP family with incomplete penetrance. Documenta ophthalmologica. Advances in ophthalmology 16 30099644
2015 Natural Functions of PLIN2 Mediating Wnt/LiCl Signaling and Glycogen Synthase Kinase 3 (GSK3)/GSK3 Substrate-Related Effects Are Modulated by Lipid. Molecular and cellular biology 16 26598603
2014 Expression of perilipin 2 (PLIN2) in porcine oocytes during maturation. Reproduction in domestic animals = Zuchthygiene 16 25131988
2024 Therapeutic siRNA targeting PLIN2 ameliorates steatosis, inflammation, and fibrosis in steatotic liver disease models. Journal of lipid research 15 39187042
1992 Autosomal dominant retinitis pigmentosa (adRP; RP6): cosegregation of RP6 and the peripherin-RDS locus in a late-onset family of Irish origin. American journal of human genetics 15 1539599
2014 The effects of IRE1, ATF6, and PERK signaling on adRP-linked rhodopsins. Advances in experimental medicine and biology 14 24664756
2023 Nuclear miR-150 enhances hepatic lipid accumulation by targeting RNA transcripts overlapping the PLIN2 promoter. iScience 13 37736048
2023 Effect on cell survival and cytoophidium assembly of the adRP-10-related IMPDH1 missense mutation Asp226Asn. Frontiers in cell and developmental biology 12 37731818
2022 An RDH-Plin2 axis modulates lipid droplet size by antagonizing Bmm lipase. EMBO reports 12 35132760
2021 Upregulated monocyte expression of PLIN2 is associated with early arterial injury in children with overweight/obesity. Atherosclerosis 12 34044206
2016 ARF1 activation dissociates ADRP from lipid droplets to promote HCV assembly. Biochemical and biophysical research communications 12 27157138
2015 Increased ADRP expression in human atherosclerotic lesions correlates with plaque instability. International journal of clinical and experimental medicine 12 26131118
1990 Further evidence of exclusion of linkage between type II autosomal dominant retinitis pigmentosa (ADRP) and D3S47 on 3q. Genomics 12 2081594
2024 Downregulation of PLIN2 in human dermal fibroblasts impairs mitochondrial function in an age-dependent fashion and induces cell senescence via GDF15. Aging cell 11 38650174
2023 A missense variant in human perilipin 2 (PLIN2 Ser251Pro) reduces hepatic steatosis in mice. JHEP reports : innovation in hepatology 11 38074507
2021 Transcriptomics analysis of Daheng broilers reveals that PLIN2 regulates chicken preadipocyte proliferation, differentiation and apoptosis. Molecular biology reports 11 34716501
2018 Molecular Findings in Families with an Initial Diagnose of Autosomal Dominant Retinitis Pigmentosa (adRP). Advances in experimental medicine and biology 11 29721949
2005 Mutational analysis of the rhodopsin gene in Chinese ADRP families by conformation sensitive gel electrophoresis. Life sciences 11 16229860
2018 Expression of APOB, ADFP and FATP1 and their correlation with fat deposition in Yunnan's top six famous chicken breeds. British poultry science 10 30004246
2005 Molecular characterization and chromosomal mapping of porcine adipose differentiation-related protein (ADRP). Journal of animal breeding and genetics = Zeitschrift fur Tierzuchtung und Zuchtungsbiologie 10 16060490
1989 Linkage analysis of human chromosome 4: exclusion of autosomal dominant retinitis pigmentosa (ADRP) and detection of new linkage groups. Cytogenetics and cell genetics 10 2572401