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Advances in ophthalmology","url":"https://pubmed.ncbi.nlm.nih.gov/30099644","citation_count":16,"is_preprint":false},{"pmid":"29893665","id":"PMC_29893665","title":"The ADRP domain from a virulent strain of infectious bronchitis virus is not sufficient to confer a pathogenic phenotype to the attenuated Beaudette strain.","date":"2018","source":"The Journal of general virology","url":"https://pubmed.ncbi.nlm.nih.gov/29893665","citation_count":16,"is_preprint":false},{"pmid":"1539599","id":"PMC_1539599","title":"Autosomal dominant retinitis pigmentosa (adRP; RP6): cosegregation of RP6 and the peripherin-RDS locus in a late-onset family of Irish origin.","date":"1992","source":"American journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/1539599","citation_count":15,"is_preprint":false},{"pmid":"35132760","id":"PMC_35132760","title":"An RDH-Plin2 axis modulates lipid droplet size by antagonizing Bmm lipase.","date":"2022","source":"EMBO 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overweight/obesity.","date":"2021","source":"Atherosclerosis","url":"https://pubmed.ncbi.nlm.nih.gov/34044206","citation_count":13,"is_preprint":false},{"pmid":"37731818","id":"PMC_37731818","title":"Effect on cell survival and cytoophidium assembly of the adRP-10-related IMPDH1 missense mutation Asp226Asn.","date":"2023","source":"Frontiers in cell and developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/37731818","citation_count":12,"is_preprint":false},{"pmid":"26131118","id":"PMC_26131118","title":"Increased ADRP expression in human atherosclerotic lesions correlates with plaque instability.","date":"2015","source":"International journal of clinical and experimental medicine","url":"https://pubmed.ncbi.nlm.nih.gov/26131118","citation_count":12,"is_preprint":false},{"pmid":"38074507","id":"PMC_38074507","title":"A missense variant in human perilipin 2 (PLIN2 Ser251Pro) reduces hepatic steatosis in mice.","date":"2023","source":"JHEP reports : innovation in hepatology","url":"https://pubmed.ncbi.nlm.nih.gov/38074507","citation_count":12,"is_preprint":false},{"pmid":"27157138","id":"PMC_27157138","title":"ARF1 activation dissociates ADRP from lipid droplets to promote HCV assembly.","date":"2016","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/27157138","citation_count":12,"is_preprint":false},{"pmid":"2081594","id":"PMC_2081594","title":"Further evidence of exclusion of linkage between type II autosomal dominant retinitis pigmentosa (ADRP) and D3S47 on 3q.","date":"1990","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/2081594","citation_count":12,"is_preprint":false},{"pmid":"37419179","id":"PMC_37419179","title":"Alcoholic Setdb1 suppression promotes hepatosteatosis in mice by strengthening Plin2.","date":"2023","source":"Metabolism: clinical and 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pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/19843633","citation_count":10,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":50365,"output_tokens":6232,"usd":0.122287,"stage1_stop_reason":"refusal"},"stage2":{"model":"","input_tokens":0,"output_tokens":0,"usd":0.0},"total_usd":0.122287,"stage1_batch_id":"msgbatch_015cW3C55o5xm8EPaM1UvcZR","stage2_batch_id":"msgbatch_018NDJHPntdYJzBohpB6hHKo","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2002,\n      \"finding\": \"PLIN2 (ADRP) localizes exclusively to the surface of neutral lipid storage droplets, and sequence/structural elements within the PAT-domain protein family are necessary and sufficient to direct association to intracellular lipid droplet surfaces, as demonstrated by GFP-tagged protein co-localization and antibody co-localization with isolated lipid droplets across mammalian, Drosophila, and Dictyostelium systems.\",\n      \"method\": \"GFP-fusion protein live-cell imaging, antibody co-localization with isolated lipid droplets, heterologous expression across species\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct localization experiments with multiple orthogonal methods (GFP tagging, antibody staining, isolated droplet fractionation) replicated across multiple species and cell types\",\n      \"pmids\": [\"12077142\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"Overexpression of GFP-ADRP (PLIN2) in murine fibroblasts increases lipid droplet number and size and significantly increases triacylglycerol content, without inducing adipocyte-specific lipogenic genes (PPARγ, LPL, acyl-CoA synthetase, FABP, FAT), indicating PLIN2 directly stimulates lipid accumulation and lipid droplet formation independently of adipogenic transcriptional programs.\",\n      \"method\": \"Adenoviral GFP-ADRP overexpression, confocal microscopy, triacylglycerol quantification, gene expression analysis\",\n      \"journal\": \"American journal of physiology. Endocrinology and metabolism\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean overexpression with functional readout (TG content) and pathway exclusion (no lipogenic gene induction), single lab\",\n      \"pmids\": [\"12217895\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"ADRP (PLIN2) expressed in transfected COS-7 cells selectively stimulates uptake of long-chain fatty acids (oleate, palmitate, arachidonate) but not medium-chain fatty acids or glucose, with increased Vmax for oleate uptake, indicating PLIN2 functions as a saturable transport component for long-chain fatty acid uptake.\",\n      \"method\": \"COS-7 cell transfection, radiolabeled fatty acid uptake kinetics (Km, Vmax determination), temperature-dependence assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional transport assay with kinetic parameters, substrate specificity established, single lab\",\n      \"pmids\": [\"10358026\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"ADRP (PLIN2) protein is degraded via the ubiquitin-proteasome pathway during regression of lipid-storing cells; proteasome inhibitor treatment abolishes ADRP decrease and accumulates polyubiquitinated ADRP, and ADRP degradation is required for triglyceride reduction.\",\n      \"method\": \"Proteasome inhibitor treatment, polyubiquitinated protein detection by immunoblot, triacsin C-induced lipid regression assay in J774 macrophages and HuH-7 liver cells\",\n      \"journal\": \"Journal of lipid research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — pharmacological and biochemical evidence of ubiquitin-proteasome degradation, two cell types, single lab\",\n      \"pmids\": [\"16230742\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"AMPK-dependent phosphorylation of PLIN2 occurs after PLIN2 interacts with the CMA chaperone HSPA8/Hsc70, and this phosphorylation is required for CMA-mediated degradation of PLIN2 from the lipid droplet surface to initiate lipolysis.\",\n      \"method\": \"AMPK inhibition/activation experiments, co-immunoprecipitation of PLIN2 with Hsc70, phosphorylation assays, CMA flux assays\",\n      \"journal\": \"Autophagy\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (kinase inhibition, co-IP, phosphorylation detection), mechanistically links AMPK to CMA substrate priming of PLIN2\",\n      \"pmids\": [\"26902588\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"PLIN2 overexpression protects lipid droplets against macroautophagy, whereas PLIN2 deficiency enhances autophagy and depletes hepatic triglyceride; in atg7-/- MEFs devoid of autophagic function, PLIN2 deficiency does not lower cellular triglyceride content, establishing that PLIN2 regulates hepatic lipid catabolism specifically through the autophagy pathway.\",\n      \"method\": \"Genetic KO (plin2-/- mice), ATG7 knockdown (adenoviral shAtg7), atg7-/- MEF cell lines, triglyceride quantification, autophagy flux assays\",\n      \"journal\": \"Autophagy\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic epistasis (PLIN2 KO × ATG7 KO double mutant) with clear pathway placement and quantitative TG readout\",\n      \"pmids\": [\"28548876\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"The E3 ubiquitin ligase TEB4 (MARCH6), a recognition component of the Ac/N-end rule pathway, directly targets the N-terminal acetyl moiety of Nα-terminally acetylated PLIN2 for polyubiquitylation and proteasomal degradation under lipid-deprived conditions, thereby reducing intracellular lipid droplet accumulation.\",\n      \"method\": \"Cycloheximide chase, in vivo ubiquitylation assay, split-Ub yeast two-hybrid, chemical cross-linking-based reciprocal co-immunoprecipitation, HeLa/HEK293T/HepG2 cell lines\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — multiple orthogonal methods (Y2H, reciprocal co-IP, in vivo ubiquitylation, chase assay) identifying specific E3 ligase and degron\",\n      \"pmids\": [\"30425097\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"MARCH6 (TEB4) E3 ligase regulates PLIN2 post-translational stability and also regulates triacylglycerol biosynthesis, thereby influencing lipid droplet abundance; identified through parallel CRISPR-Cas9 loss-of-function screens using genome-edited PLIN2 reporter cell lines.\",\n      \"method\": \"CRISPR-Cas9 genome-wide loss-of-function screens, PLIN2-reporter cell lines (multiple human cell types), functional validation of MARCH6 on TG biosynthesis\",\n      \"journal\": \"Developmental cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genome-scale CRISPR screens replicated across cell types with functional follow-up on MARCH6-PLIN2 axis\",\n      \"pmids\": [\"37494933\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"ADP-ribosylation factor 1 (ARF1) binds directly to a central domain of ADRP (PLIN2) that is dispensable for lipid droplet binding; GDP-bound ARF1 preferentially interacts with ADRP and induces its dissociation from the lipid droplet surface; brefeldin A or dominant-negative ARF1 causes ADRP dissociation from lipid droplets.\",\n      \"method\": \"Yeast two-hybrid screening, GST pull-down, co-immunoprecipitation, dominant-negative ARF1 expression, brefeldin A treatment, ADRP deletion mutant mapping\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — yeast two-hybrid confirmed by GST pull-down and co-IP, deletion mapping of interaction domain, pharmacological and genetic validation of functional consequence\",\n      \"pmids\": [\"15336557\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"CGI-58 (the Chanarin-Dorfman syndrome gene product) was identified as an interaction partner for both perilipin and ADRP (PLIN2) by yeast two-hybrid screening; the ADRP-CGI-58 interaction was identified by Y2H; IRG-47 was identified as an ADRP-specific binding partner.\",\n      \"method\": \"Yeast two-hybrid screening, GST pull-down (for perilipin-CGI-58), fluorescence microscopy co-localization\",\n      \"journal\": \"Molecular and cellular biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — Y2H for ADRP-CGI-58 interaction (GST pull-down confirmed only for perilipin-CGI-58, not ADRP specifically); single lab\",\n      \"pmids\": [\"16532261\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Live-cell FRET analysis demonstrated that PLIN2 directly interacts with phosphatidylcholine, sphingomyelin, stearic acid, and cholesterol on the surface of lipid droplets at molecular distances of 44–57 Å; PLIN2 overexpression increases triacylglycerol, fatty acid, cholesteryl ester, and total phospholipid content and upregulates enzymes involved in their synthesis while decreasing lipolytic enzyme expression.\",\n      \"method\": \"Live-cell FRET (CFP-Plin2 with fluorescent lipid probes), pixel-by-pixel FRET efficiency mapping, lipid quantification, enzyme expression analysis\",\n      \"journal\": \"American journal of physiology. Cell physiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — direct molecular contact demonstrated by quantitative FRET with distance calculations, functional consequences measured, single lab\",\n      \"pmids\": [\"22744009\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"ADRP (PLIN2) demonstrates saturable, high-affinity binding to sphingomyelin and phosphatidylcholine (nanomolar range Kd) in fluorescence binding assays using lipid droplet fractions, identifying ADRP as a phospholipid-binding protein on the lipid droplet surface.\",\n      \"method\": \"Fluorescence binding assays with NBD-sphingomyelin and NBD-phosphatidylcholine, lipid droplet fractionation, Kd determination\",\n      \"journal\": \"Lipids\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vitro binding assay with quantitative affinity measurement, single lab, single method\",\n      \"pmids\": [\"20473576\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"The missense polymorphism Ser251Pro in PLIN2 disrupts a predicted α-helix; macrophages and HEK293 cells stably expressing the Pro251 variant show increased lipid accumulation, decreased lipolysis, increased number of small lipid droplets per cell, and increased perilipin 3 expression compared with Ser251 cells.\",\n      \"method\": \"Structure modeling (3D-JigSaw/Chimera), stable HEK293 transfection with each allele, macrophage assays from human carriers, lipid droplet size distribution analysis, lipolysis assays\",\n      \"journal\": \"FASEB journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — structural modeling plus functional cell assays in both primary human macrophages and stable transfected cell lines, with multiple phenotypic readouts\",\n      \"pmids\": [\"23603836\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Plin2 inhibits insulin-mediated glucose uptake by interacting directly with SNAP23 (a SNARE protein) on lipid droplets (FRET distance ~51 Å), increasing SNAP23 targeting to lipid droplets and decreasing its availability for GLUT4 vesicle fusion; PLIN2 knockdown conversely increases glucose uptake.\",\n      \"method\": \"Overexpression and RNAi knockdown of Plin2, 2-NBD-glucose and [3H]-2-deoxyglucose uptake assays, FRET, co-immunoprecipitation, co-localization microscopy in L cells and 3T3-L1 cells\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal co-IP + FRET for protein interaction, bidirectional genetic manipulation (OE and KD) with direct functional glucose uptake assay\",\n      \"pmids\": [\"24040030\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"In ADFP (PLIN2) null embryonic cells, Tip47/PLIN3 compensates as the sole lipid droplet-associated PAT protein; knockdown of Tip47 in ADFP null cells impairs lipid droplet formation and shifts exogenous NEFA utilization from triglycerides to phospholipids, demonstrating that PLIN2 and PLIN3 regulate the balance between triglyceride and phospholipid synthesis from exogenous fatty acids.\",\n      \"method\": \"ADFP null cell lines from KO mice, Tip47 siRNA knockdown, mass spectrometry identification of LD proteins, immunoblot, immunocytochemistry, NEFA uptake assay, lipolysis assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic null cells plus siRNA double knockdown, MS identification, multiple functional readouts (lipid droplet formation, NEFA uptake, lipolysis, lipid class analysis)\",\n      \"pmids\": [\"16968708\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Rab18 is translocated from the ER to lipid droplets during lipid droplet accumulation in a PLIN2-dependent manner; Rab18 binds directly to the C-terminus of PLIN2, and LD-associated Rab18 further recruits ACSL3 to lipid droplets, forming a PLIN2-Rab18-ACSL3 complex that promotes LD accumulation and dynamics in myoblasts.\",\n      \"method\": \"Co-immunoprecipitation, PLIN2 depletion (siRNA), Rab18 overexpression/loss-of-function, ACSL3 localization assay in C2C12 cells, triglyceride quantification\",\n      \"journal\": \"Biochimica et biophysica acta. Molecular and cell biology of lipids\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP identifies complex, PLIN2 depletion establishes epistasis for Rab18 LD localization, C-terminus mapping; single lab\",\n      \"pmids\": [\"33713834\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Plin2 deficiency in mouse heart causes increased triglyceride accumulation in cardiomyocytes due to reduced lipophagy (not increased lipid synthesis), and Plin2-/- mice show reduced cardiac output after myocardial infarction, establishing Plin2 as necessary for proper lipophagic hydrolysis of cardiac lipid droplets.\",\n      \"method\": \"Plin2-/- mouse model, triglyceride quantification, lipophagy flux assays, echocardiography before and after myocardial infarction\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic KO with mechanistic lipophagy flux assay and in vivo cardiac functional readout; single lab\",\n      \"pmids\": [\"31061399\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"In liver-specific PLIN2 knockout mice, protection against NAFLD is driven by integrated actions of both ATGL (cytosolic lipase) and lipophagy; inhibition of either pathway alone blunted increased fatty acid oxidation in PLIN2LKO hepatocytes, and combined inhibition had no additive effect, indicating the two pathways converge on the same lipid droplet TAG pool.\",\n      \"method\": \"Liver-specific PLIN2 KO mice, ATGL pharmacological inhibition, autophagy inhibition, p62 flux assay, LC3-positive vesicle quantification, fatty acid oxidation measurement in primary hepatocytes\",\n      \"journal\": \"Cells\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — liver-specific genetic KO combined with pharmacological inhibitors and autophagic flux assays; mechanistic epistasis between PLIN2, ATGL, and lipophagy established\",\n      \"pmids\": [\"33923083\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"PLIN2 modulates the unfolded protein response and ER stress resolution in pancreatic β cells; PLIN2 downregulation ameliorates fatty acid- and chemical-induced ER stress and is associated with enhanced autophagic flux; PLIN2 ablation in Akita diabetic mice mitigates ER stress, reduces β-cell apoptosis, and partially restores β-cell mass.\",\n      \"method\": \"PLIN2 siRNA knockdown, PLIN2 overexpression, Plin2-/- × Akita mouse genetic cross, ER stress markers (UPR), autophagic flux assays, β-cell mass quantification, apoptosis assays\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — bidirectional genetic manipulation in vitro (siRNA/OE) and in vivo (double KO mouse) with multiple mechanistic readouts (UPR, autophagy flux, apoptosis, cell mass)\",\n      \"pmids\": [\"28102311\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Upon exit from pluripotency in embryonic stem cells, Plin2 is recognized by Hsc70 and degraded via chaperone-mediated autophagy (CMA) to facilitate lipid droplet mobilization; excessive lipid hydrolysis caused by Plin2 knockout induces lipidomic remodeling (decreased cardiolipin and phosphatidylethanolamine), mitochondrial cristae defects, reduced acetyl-CoA, and diminished histone acetylation, linking LD homeostasis to epigenetic regulation.\",\n      \"method\": \"Plin2 KO ESCs, ATGL inhibition rescue, lipidomics, mitochondrial morphology (electron microscopy), acetyl-CoA quantification, histone acetylation ChIP, CMA assay with Hsc70 co-IP\",\n      \"journal\": \"Cell death and differentiation\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic KO with ATGL inhibitor epistasis rescue, multi-omic readouts (lipidomics, metabolomics, ChIP), Hsc70 co-IP establishing CMA mechanism\",\n      \"pmids\": [\"35614132\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"The human ADFP (PLIN2) gene is a direct transcriptional target of LXR; the partial LXR agonist GW3965 (but not the full agonist T0901317) induces ADFP expression in primary human hepatocytes by binding to functional LXR response elements (LXREs) in the 3'-UTR and 5'-flanking regions, recruiting RNA polymerase II and CBP/p300 coactivators.\",\n      \"method\": \"Chromatin immunoprecipitation (ChIP), luciferase reporter assays, bioinformatics identification of LXREs, primary human hepatocyte treatment\",\n      \"journal\": \"Molecular pharmacology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — ChIP demonstrates direct LXR binding at specific LXREs, luciferase reporter validates functional transcriptional activation, primary human cells; single lab\",\n      \"pmids\": [\"19843633\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"ADRP (PLIN2) expression in RAW264.7 macrophages is conjointly regulated by PU.1 and AP-1 transcription factors binding to an Ets/AP-1 element in the ADRP promoter; PI3 kinase activity is required for PMA-induced ADRP mRNA expression and promoter activity via PU.1/AP-1 complex formation.\",\n      \"method\": \"Promoter deletion/mutation reporter assays, EMSA (PU.1/AP-1 complex), PI3 kinase inhibitor treatment, PMA stimulation assays\",\n      \"journal\": \"Journal of biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — EMSA identifies transcription factor binding, promoter mutation confirms functional Ets/AP-1 element, PI3K inhibitor links signaling to complex formation; single lab\",\n      \"pmids\": [\"16272134\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Oleic acid-induced ADRP expression requires both the AP-1 site and PPAR response element (PPRE) in the ADRP promoter; AP-1 mutation abolishes oleic acid-stimulated promoter activity while PPAR ligands retain activity; Pycnogenol suppresses ADRP expression in NMuLi liver cells by accelerating ADRP mRNA degradation rather than inhibiting promoter activity or AP-1 binding.\",\n      \"method\": \"Promoter mutation luciferase assays, DNA binding assays (AP-1), mRNA half-life measurement with actinomycin D, Pycnogenol treatment\",\n      \"journal\": \"American journal of physiology. Endocrinology and metabolism\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — promoter mutagenesis with luciferase readout, mRNA stability assay, dissects two independent regulatory mechanisms; single lab\",\n      \"pmids\": [\"19383873\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"SARS-CoV-2 nucleocapsid protein drives DGAT1/2 gene expression to facilitate lipid droplet formation and associates directly with ADRP (PLIN2) on the lipid droplet surface to complete the viral replication cycle; DGAT gene depletion reduces SARS-CoV-2 protein synthesis without affecting genome","stage2_raw":"","audit_flag":{"gene":"PLIN2","tier":"GROUNDING","verdict":"Evidence-grounding concern","subtype":"recall_miss","uniprot_band":"sparse","rules_fired":"R5","issue":"R5: no narrative despite experimental UniProt FUNCTION (117 chars) and on-target evidence in corpus (100 on-target corpus titles)"},"evaluation":null}