{"gene":"OSBPL10","run_date":"2026-06-10T05:19:53","timeline":{"discoveries":[{"year":2009,"finding":"ORP10 (encoded by OSBPL10) suppresses hepatic lipogenesis and VLDL production: silencing OSBPL10 in Huh7 cells increased incorporation of [3H]acetate into cholesterol and both [3H]acetate and [3H]oleate into triglycerides, and enhanced secreted apolipoprotein B100 accumulation in growth medium.","method":"siRNA silencing in human hepatoma cells (Huh7) with radiolabeled lipid incorporation assays and apolipoprotein B100 secretion measurement","journal":"Journal of molecular medicine (Berlin, Germany)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean knockdown with multiple orthogonal functional readouts (lipid synthesis assays + ApoB secretion), single lab","pmids":["19554302"],"is_preprint":false},{"year":2009,"finding":"ORP10 associates dynamically with microtubules, consistent with a role in intracellular transport or organelle positioning.","method":"Cellular imaging/co-localization of ORP10 with microtubules in Huh7 cells","journal":"Journal of molecular medicine (Berlin, Germany)","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single imaging-based method, no functional consequence directly linked","pmids":["19554302"],"is_preprint":false},{"year":2017,"finding":"OSBPL10 knockdown in THP-1 cells by shRNA leads to a significant reduction in dengue virus (DENV2) replication, establishing a direct functional role for OSBPL10 in supporting dengue virus replication in macrophage-like cells.","method":"shRNA knockdown in THP-1 cells followed by DENV2 infection and viral replication quantification","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — two independent shRNAs used in loss-of-function experiment with defined viral replication readout, single lab","pmids":["28241052"],"is_preprint":false},{"year":2024,"finding":"Hypoxia induces OSBPL10 expression through direct interaction between HIF-1α and the OSBPL10 promoter region; OSBPL10 in turn directly binds CNBP (CCHC-type zinc finger nucleic acid binding protein), mediating CNBP expression to regulate pancreatic cancer cell proliferation, metastasis, and macrophage polarization (M1→M2).","method":"Co-immunoprecipitation, mass spectrometry, western blot, promoter interaction assay (HIF-1α binding), and functional cell assays in pancreatic cancer cells","journal":"BioFactors (Oxford, England)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP confirmed by mass spectrometry plus western blot for binding partner identification, HIF-1α promoter interaction shown, single lab","pmids":["39329194"],"is_preprint":false},{"year":2026,"finding":"OSBPL10 transfers phosphatidylserine (PS) to lysosomes to mediate lysosomal membrane repair after spinal cord injury; OSBPL10 overexpression alleviates lysosomal membrane permeabilization, restores autophagic flux, and reduces ferroptosis and oxidative stress in neurons, as confirmed by molecular docking and rescue experiments with lipid synthesis inhibitors.","method":"Western blotting, immunofluorescence, molecular docking, rescue experiments with lipid synthesis inhibitors, RNA sequencing, ELISA (human CSF), and in vivo mouse SCI model (BMS, Nissl staining, gait analysis)","journal":"Journal of neuroinflammation","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (molecular docking, lipid inhibitor rescue, in vivo functional assays), single lab","pmids":["41794746"],"is_preprint":false},{"year":2026,"finding":"OSBPL10 functionally cooperates with VAPA/VAPB to facilitate rapid lysosomal repair via ATG2A, thereby promoting lipophagy (autophagic degradation of lipid droplets) and lipid mobilization in pancreatic ductal adenocarcinoma; inhibition of lysosomal function abrogated the pro-lipophagic and pro-tumorigenic effects of OSBPL10.","method":"Immunofluorescence, single-cell transcriptomics, orthotopic and subcutaneous xenograft models, lysosomal function inhibition experiments, and mechanistic co-factor analysis (VAPA/VAPB, ATG2A)","journal":"International journal of biological sciences","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo xenograft models plus mechanistic pathway dissection (VAPA/VAPB/ATG2A), single lab","pmids":["42003919"],"is_preprint":false}],"current_model":"OSBPL10 encodes ORP10, a lipid transfer protein that suppresses hepatic lipogenesis and VLDL production, associates with microtubules, transfers phosphatidylserine to lysosomes to mediate lysosomal membrane repair (promoting autophagic flux and preventing ferroptosis), cooperates with VAPA/VAPB and ATG2A to drive lipophagy, is transcriptionally induced by HIF-1α under hypoxia and signals through direct binding to CNBP, and supports dengue virus replication in macrophage-like cells."},"narrative":{"mechanistic_narrative":"OSBPL10 encodes ORP10, a lipid transfer protein that controls cellular lipid distribution with consequences for hepatic lipid metabolism, lysosomal integrity, and tumor biology [PMID:19554302, PMID:41794746]. In hepatoma cells, ORP10 suppresses lipogenesis and VLDL output, restraining cholesterol and triglyceride synthesis and apolipoprotein B100 secretion [PMID:19554302]. Mechanistically, ORP10 transfers phosphatidylserine to lysosomes to repair lysosomal membranes, an activity that restores autophagic flux and limits ferroptosis and oxidative stress in injured neurons [PMID:41794746]. This lysosomal-repair function operates in cooperation with VAPA/VAPB and ATG2A to drive lipophagy and lipid mobilization, supporting tumor growth in pancreatic ductal adenocarcinoma [PMID:42003919]. OSBPL10 is transcriptionally induced by HIF-1α under hypoxia and acts through direct binding to CNBP to influence pancreatic cancer proliferation, metastasis, and macrophage M1→M2 polarization [PMID:39329194], and it is also required to support dengue virus replication in macrophage-like cells [PMID:28241052].","teleology":[{"year":2009,"claim":"Establishing the first cellular function of ORP10 showed it acts as a negative regulator of hepatic lipid synthesis rather than a passive lipid binder.","evidence":"siRNA silencing in Huh7 hepatoma cells with radiolabeled lipid incorporation assays and ApoB100 secretion measurement","pmids":["19554302"],"confidence":"Medium","gaps":["Did not identify the lipid transfer reaction or molecular partner responsible for lipogenic suppression","Mechanism linking ORP10 to ApoB100 secretion not resolved"]},{"year":2009,"claim":"Imaging placed ORP10 on microtubules, hinting at a role in intracellular transport or organelle positioning.","evidence":"Co-localization imaging of ORP10 with microtubules in Huh7 cells","pmids":["19554302"],"confidence":"Low","gaps":["Single imaging-based observation with no functional consequence linked","No demonstration that microtubule association is required for any ORP10 activity"]},{"year":2017,"claim":"Loss-of-function screening revealed OSBPL10 is required by a virus, expanding its role beyond lipid metabolism into host-pathogen interaction.","evidence":"Two independent shRNAs in THP-1 macrophage-like cells followed by DENV2 infection and viral replication quantification","pmids":["28241052"],"confidence":"Medium","gaps":["Molecular step in the viral life cycle requiring OSBPL10 not defined","Whether lipid transfer activity underlies the pro-viral effect untested"]},{"year":2024,"claim":"Defining an upstream and downstream axis showed OSBPL10 is a HIF-1α target that signals via direct CNBP binding to drive pancreatic cancer phenotypes and macrophage polarization.","evidence":"HIF-1α promoter interaction assay, Co-IP with mass spectrometry, western blot, and functional cell assays in pancreatic cancer cells","pmids":["39329194"],"confidence":"Medium","gaps":["Co-IP/MS not reciprocally validated","Mechanism connecting CNBP regulation to metastasis and M1→M2 polarization not fully resolved"]},{"year":2026,"claim":"Identifying phosphatidylserine delivery to lysosomes established the concrete lipid transfer activity of OSBPL10 and tied it to lysosomal membrane repair, autophagy, and protection from ferroptosis.","evidence":"Western blotting, immunofluorescence, molecular docking, lipid synthesis inhibitor rescue, RNA-seq, CSF ELISA, and an in vivo mouse spinal cord injury model","pmids":["41794746"],"confidence":"Medium","gaps":["Direct in vitro reconstitution of PS transfer not shown","Lysosomal membrane contact site machinery for PS delivery not detailed"]},{"year":2026,"claim":"Mapping co-factors placed OSBPL10's lysosomal repair within a VAPA/VAPB–ATG2A axis driving lipophagy and tumor growth, unifying its lysosomal and lipid-mobilization roles.","evidence":"Immunofluorescence, single-cell transcriptomics, orthotopic/subcutaneous xenografts, and lysosomal function inhibition in PDAC","pmids":["42003919"],"confidence":"Medium","gaps":["Direct physical interaction stoichiometry among OSBPL10, VAPA/VAPB and ATG2A not quantified","Whether contact-site assembly is constitutive or repair-triggered unknown"]},{"year":null,"claim":"How OSBPL10's microtubule association, hepatic lipogenic suppression, viral support, and lysosomal PS transfer mechanistically converge on a single lipid transfer mechanism remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unified biochemical model connecting the distinct cellular contexts","Structural basis of lipid selectivity and membrane targeting uncharacterized"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008289","term_label":"lipid binding","supporting_discovery_ids":[0,4]},{"term_id":"GO:0140104","term_label":"molecular carrier activity","supporting_discovery_ids":[4,5]}],"localization":[{"term_id":"GO:0005764","term_label":"lysosome","supporting_discovery_ids":[4,5]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[1]}],"pathway":[{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[4,5]},{"term_id":"R-HSA-1430728","term_label":"Metabolism","supporting_discovery_ids":[0]}],"complexes":[],"partners":["CNBP","VAPA","VAPB","ATG2A"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9BXB5","full_name":"Oxysterol-binding protein-related protein 10","aliases":[],"length_aa":764,"mass_kda":84.0,"function":"Probable lipid transporter involved in lipid countertransport between the endoplasmic reticulum and the plasma membrane. Its ability to bind phosphatidylserine, suggests that it specifically exchanges phosphatidylserine with phosphatidylinositol 4-phosphate (PI4P), delivering phosphatidylserine to the plasma membrane in exchange for PI4P (Probable) (PubMed:23934110). Plays a role in negative regulation of lipid biosynthesis (PubMed:19554302). Negatively regulates APOB secretion from hepatocytes (PubMed:19554302, PubMed:22906437). Binds cholesterol and acidic phospholipids (PubMed:22906437). Also binds 25-hydroxycholesterol (PubMed:17428193). Binds phosphatidylserine (PubMed:23934110)","subcellular_location":"Cytoplasm, cytoskeleton","url":"https://www.uniprot.org/uniprotkb/Q9BXB5/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/OSBPL10","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"OSBPL11","stoichiometry":0.2},{"gene":"VAPA","stoichiometry":0.2},{"gene":"VAPB","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/OSBPL10","total_profiled":1310},"omim":[{"mim_id":"606739","title":"OXYSTEROL-BINDING PROTEIN-LIKE PROTEIN 11; OSBPL11","url":"https://www.omim.org/entry/606739"},{"mim_id":"606738","title":"OXYSTEROL-BINDING PROTEIN-LIKE PROTEIN 10; OSBPL10","url":"https://www.omim.org/entry/606738"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Golgi apparatus","reliability":"Approved"},{"location":"Plasma membrane","reliability":"Approved"},{"location":"Nucleoplasm","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/OSBPL10"},"hgnc":{"alias_symbol":[],"prev_symbol":[]},"alphafold":{"accession":"Q9BXB5","domains":[{"cath_id":"2.30.29.30","chopping":"78-179","consensus_level":"high","plddt":87.0197,"start":78,"end":179},{"cath_id":"2.40.160.120","chopping":"381-500_523-757","consensus_level":"medium","plddt":90.5943,"start":381,"end":757}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BXB5","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BXB5-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BXB5-F1-predicted_aligned_error_v6.png","plddt_mean":73.31},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=OSBPL10","jax_strain_url":"https://www.jax.org/strain/search?query=OSBPL10"},"sequence":{"accession":"Q9BXB5","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9BXB5.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9BXB5/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BXB5"}},"corpus_meta":[{"pmid":"28241052","id":"PMC_28241052","title":"OSBPL10, RXRA and lipid metabolism confer African-ancestry protection against dengue haemorrhagic fever in admixed Cubans.","date":"2017","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/28241052","citation_count":62,"is_preprint":false},{"pmid":"19554302","id":"PMC_19554302","title":"OSBPL10, a novel candidate gene for high triglyceride trait in dyslipidemic Finnish subjects, regulates cellular lipid metabolism.","date":"2009","source":"Journal of molecular medicine (Berlin, Germany)","url":"https://pubmed.ncbi.nlm.nih.gov/19554302","citation_count":53,"is_preprint":false},{"pmid":"20224571","id":"PMC_20224571","title":"Variation in OSBPL10 is associated with dyslipidemia.","date":"2010","source":"Hypertension research : official journal of the Japanese Society of Hypertension","url":"https://pubmed.ncbi.nlm.nih.gov/20224571","citation_count":17,"is_preprint":false},{"pmid":"39329194","id":"PMC_39329194","title":"OSBPL10-CNBP axis mediates hypoxia-induced pancreatic cancer development.","date":"2024","source":"BioFactors (Oxford, England)","url":"https://pubmed.ncbi.nlm.nih.gov/39329194","citation_count":7,"is_preprint":false},{"pmid":"35180547","id":"PMC_35180547","title":"Silencing of circ_OSBPL10 affects the functional behaviors of oral squamous cell carcinoma cells by the miR-299-3p/CDK6 axis.","date":"2022","source":"Archives of oral biology","url":"https://pubmed.ncbi.nlm.nih.gov/35180547","citation_count":4,"is_preprint":false},{"pmid":"41794746","id":"PMC_41794746","title":"OSBPL10 alleviates neuronal ferroptosis via lysosomal membrane repair in a PS-dependent manner after spinal cord injury.","date":"2026","source":"Journal of neuroinflammation","url":"https://pubmed.ncbi.nlm.nih.gov/41794746","citation_count":0,"is_preprint":false},{"pmid":"42003919","id":"PMC_42003919","title":"OSBPL10 Drives Lipophagy-Mediated Lipid Mobilization to Promote Pancreatic Ductal Adenocarcinoma Progression.","date":"2026","source":"International journal of biological sciences","url":"https://pubmed.ncbi.nlm.nih.gov/42003919","citation_count":0,"is_preprint":false},{"pmid":"41945956","id":"PMC_41945956","title":"DNA Alterations in the Upstream Region of Exon 1 of OSBPL10 in Northern Thai Patients with Diffuse Large B-Cell Lymphoma.","date":"2026","source":"Asian Pacific journal of cancer prevention : APJCP","url":"https://pubmed.ncbi.nlm.nih.gov/41945956","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6849,"output_tokens":1562,"usd":0.021989,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8364,"output_tokens":2352,"usd":0.05031,"stage2_stop_reason":"end_turn"},"total_usd":0.072299,"stage1_batch_id":"msgbatch_013a8chtv3AWyTqv4z4sEF4C","stage2_batch_id":"msgbatch_01AHsuW63vinsvuTgzmQ3n62","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2009,\n      \"finding\": \"ORP10 (encoded by OSBPL10) suppresses hepatic lipogenesis and VLDL production: silencing OSBPL10 in Huh7 cells increased incorporation of [3H]acetate into cholesterol and both [3H]acetate and [3H]oleate into triglycerides, and enhanced secreted apolipoprotein B100 accumulation in growth medium.\",\n      \"method\": \"siRNA silencing in human hepatoma cells (Huh7) with radiolabeled lipid incorporation assays and apolipoprotein B100 secretion measurement\",\n      \"journal\": \"Journal of molecular medicine (Berlin, Germany)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean knockdown with multiple orthogonal functional readouts (lipid synthesis assays + ApoB secretion), single lab\",\n      \"pmids\": [\"19554302\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"ORP10 associates dynamically with microtubules, consistent with a role in intracellular transport or organelle positioning.\",\n      \"method\": \"Cellular imaging/co-localization of ORP10 with microtubules in Huh7 cells\",\n      \"journal\": \"Journal of molecular medicine (Berlin, Germany)\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single imaging-based method, no functional consequence directly linked\",\n      \"pmids\": [\"19554302\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"OSBPL10 knockdown in THP-1 cells by shRNA leads to a significant reduction in dengue virus (DENV2) replication, establishing a direct functional role for OSBPL10 in supporting dengue virus replication in macrophage-like cells.\",\n      \"method\": \"shRNA knockdown in THP-1 cells followed by DENV2 infection and viral replication quantification\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — two independent shRNAs used in loss-of-function experiment with defined viral replication readout, single lab\",\n      \"pmids\": [\"28241052\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Hypoxia induces OSBPL10 expression through direct interaction between HIF-1α and the OSBPL10 promoter region; OSBPL10 in turn directly binds CNBP (CCHC-type zinc finger nucleic acid binding protein), mediating CNBP expression to regulate pancreatic cancer cell proliferation, metastasis, and macrophage polarization (M1→M2).\",\n      \"method\": \"Co-immunoprecipitation, mass spectrometry, western blot, promoter interaction assay (HIF-1α binding), and functional cell assays in pancreatic cancer cells\",\n      \"journal\": \"BioFactors (Oxford, England)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP confirmed by mass spectrometry plus western blot for binding partner identification, HIF-1α promoter interaction shown, single lab\",\n      \"pmids\": [\"39329194\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"OSBPL10 transfers phosphatidylserine (PS) to lysosomes to mediate lysosomal membrane repair after spinal cord injury; OSBPL10 overexpression alleviates lysosomal membrane permeabilization, restores autophagic flux, and reduces ferroptosis and oxidative stress in neurons, as confirmed by molecular docking and rescue experiments with lipid synthesis inhibitors.\",\n      \"method\": \"Western blotting, immunofluorescence, molecular docking, rescue experiments with lipid synthesis inhibitors, RNA sequencing, ELISA (human CSF), and in vivo mouse SCI model (BMS, Nissl staining, gait analysis)\",\n      \"journal\": \"Journal of neuroinflammation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (molecular docking, lipid inhibitor rescue, in vivo functional assays), single lab\",\n      \"pmids\": [\"41794746\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"OSBPL10 functionally cooperates with VAPA/VAPB to facilitate rapid lysosomal repair via ATG2A, thereby promoting lipophagy (autophagic degradation of lipid droplets) and lipid mobilization in pancreatic ductal adenocarcinoma; inhibition of lysosomal function abrogated the pro-lipophagic and pro-tumorigenic effects of OSBPL10.\",\n      \"method\": \"Immunofluorescence, single-cell transcriptomics, orthotopic and subcutaneous xenograft models, lysosomal function inhibition experiments, and mechanistic co-factor analysis (VAPA/VAPB, ATG2A)\",\n      \"journal\": \"International journal of biological sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo xenograft models plus mechanistic pathway dissection (VAPA/VAPB/ATG2A), single lab\",\n      \"pmids\": [\"42003919\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"OSBPL10 encodes ORP10, a lipid transfer protein that suppresses hepatic lipogenesis and VLDL production, associates with microtubules, transfers phosphatidylserine to lysosomes to mediate lysosomal membrane repair (promoting autophagic flux and preventing ferroptosis), cooperates with VAPA/VAPB and ATG2A to drive lipophagy, is transcriptionally induced by HIF-1α under hypoxia and signals through direct binding to CNBP, and supports dengue virus replication in macrophage-like cells.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"OSBPL10 encodes ORP10, a lipid transfer protein that controls cellular lipid distribution with consequences for hepatic lipid metabolism, lysosomal integrity, and tumor biology [#0, #4]. In hepatoma cells, ORP10 suppresses lipogenesis and VLDL output, restraining cholesterol and triglyceride synthesis and apolipoprotein B100 secretion [#0]. Mechanistically, ORP10 transfers phosphatidylserine to lysosomes to repair lysosomal membranes, an activity that restores autophagic flux and limits ferroptosis and oxidative stress in injured neurons [#4]. This lysosomal-repair function operates in cooperation with VAPA/VAPB and ATG2A to drive lipophagy and lipid mobilization, supporting tumor growth in pancreatic ductal adenocarcinoma [#5]. OSBPL10 is transcriptionally induced by HIF-1\\u03b1 under hypoxia and acts through direct binding to CNBP to influence pancreatic cancer proliferation, metastasis, and macrophage M1\\u2192M2 polarization [#3], and it is also required to support dengue virus replication in macrophage-like cells [#2].\",\n  \"teleology\": [\n    {\n      \"year\": 2009,\n      \"claim\": \"Establishing the first cellular function of ORP10 showed it acts as a negative regulator of hepatic lipid synthesis rather than a passive lipid binder.\",\n      \"evidence\": \"siRNA silencing in Huh7 hepatoma cells with radiolabeled lipid incorporation assays and ApoB100 secretion measurement\",\n      \"pmids\": [\"19554302\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Did not identify the lipid transfer reaction or molecular partner responsible for lipogenic suppression\", \"Mechanism linking ORP10 to ApoB100 secretion not resolved\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Imaging placed ORP10 on microtubules, hinting at a role in intracellular transport or organelle positioning.\",\n      \"evidence\": \"Co-localization imaging of ORP10 with microtubules in Huh7 cells\",\n      \"pmids\": [\"19554302\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single imaging-based observation with no functional consequence linked\", \"No demonstration that microtubule association is required for any ORP10 activity\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Loss-of-function screening revealed OSBPL10 is required by a virus, expanding its role beyond lipid metabolism into host-pathogen interaction.\",\n      \"evidence\": \"Two independent shRNAs in THP-1 macrophage-like cells followed by DENV2 infection and viral replication quantification\",\n      \"pmids\": [\"28241052\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular step in the viral life cycle requiring OSBPL10 not defined\", \"Whether lipid transfer activity underlies the pro-viral effect untested\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Defining an upstream and downstream axis showed OSBPL10 is a HIF-1\\u03b1 target that signals via direct CNBP binding to drive pancreatic cancer phenotypes and macrophage polarization.\",\n      \"evidence\": \"HIF-1\\u03b1 promoter interaction assay, Co-IP with mass spectrometry, western blot, and functional cell assays in pancreatic cancer cells\",\n      \"pmids\": [\"39329194\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Co-IP/MS not reciprocally validated\", \"Mechanism connecting CNBP regulation to metastasis and M1\\u2192M2 polarization not fully resolved\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Identifying phosphatidylserine delivery to lysosomes established the concrete lipid transfer activity of OSBPL10 and tied it to lysosomal membrane repair, autophagy, and protection from ferroptosis.\",\n      \"evidence\": \"Western blotting, immunofluorescence, molecular docking, lipid synthesis inhibitor rescue, RNA-seq, CSF ELISA, and an in vivo mouse spinal cord injury model\",\n      \"pmids\": [\"41794746\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct in vitro reconstitution of PS transfer not shown\", \"Lysosomal membrane contact site machinery for PS delivery not detailed\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Mapping co-factors placed OSBPL10's lysosomal repair within a VAPA/VAPB\\u2013ATG2A axis driving lipophagy and tumor growth, unifying its lysosomal and lipid-mobilization roles.\",\n      \"evidence\": \"Immunofluorescence, single-cell transcriptomics, orthotopic/subcutaneous xenografts, and lysosomal function inhibition in PDAC\",\n      \"pmids\": [\"42003919\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct physical interaction stoichiometry among OSBPL10, VAPA/VAPB and ATG2A not quantified\", \"Whether contact-site assembly is constitutive or repair-triggered unknown\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How OSBPL10's microtubule association, hepatic lipogenic suppression, viral support, and lysosomal PS transfer mechanistically converge on a single lipid transfer mechanism remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No unified biochemical model connecting the distinct cellular contexts\", \"Structural basis of lipid selectivity and membrane targeting uncharacterized\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008289\", \"supporting_discovery_ids\": [0, 4]},\n      {\"term_id\": \"GO:0140104\", \"supporting_discovery_ids\": [4, 5]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005764\", \"supporting_discovery_ids\": [4, 5]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [4, 5]},\n      {\"term_id\": \"R-HSA-1430728\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"CNBP\", \"VAPA\", \"VAPB\", \"ATG2A\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}