{"gene":"STARD10","run_date":"2026-06-10T07:46:42","timeline":{"discoveries":[{"year":2005,"finding":"StarD10 functions as a phospholipid transfer protein, selectively binding and transferring phosphatidylcholine (PC) and phosphatidylethanolamine (PE) between membranes. Binding specificity was demonstrated by ESR, FRET-based assays, and selective extraction from radiolabeled vesicles. Mass spectrometry revealed preference for lipid species with palmitoyl/stearoyl at sn-1 and unsaturated fatty acyl chain at sn-2. In vivo lipid binding was confirmed by photoactivatable PC cross-linking in HEK-293T cells. This distinguishes StarD10 from related START domain proteins Pctp and CERT.","method":"Electron spin resonance, FRET-based lipid binding assay, radiolabeled lipid extraction, mass spectrometry, photoactivatable lipid cross-linking in transfected cells","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — multiple orthogonal in vitro biochemical assays plus in vivo cross-linking, single rigorous study","pmids":["15911624"],"is_preprint":false},{"year":2004,"finding":"StarD10 is a phosphoprotein overexpressed in ErbB2-positive breast tumors; coexpression of StarD10 with ErbB1/EGFR in murine fibroblasts enhanced anchorage-independent growth in soft agar, demonstrating functional cooperation between StarD10 and ErbB receptor signaling.","method":"Soft agar anchorage-independent growth assay, co-expression in murine fibroblasts, biochemical purification and phosphoserine antibody cross-reactivity","journal":"Cancer research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — defined cellular phenotype by loss/gain-of-function in a relevant assay, single lab but multiple methods","pmids":["15150109"],"is_preprint":false},{"year":2005,"finding":"StarD10 was identified as a phosphoprotein; a phosphorylation site at Ser-259 was identified by tandem mass spectrometry of immunoaffinity-purified Flag-tagged StarD10 from HEK-293T cells.","method":"Immunoaffinity purification, IMAC enrichment of phosphopeptides, tandem mass spectrometry","journal":"Electrophoresis","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — single lab, single method (MS-based phosphosite identification), no functional validation of this specific site in this paper","pmids":["15704244"],"is_preprint":false},{"year":2007,"finding":"StarD10 is phosphorylated in vivo at serine 284 by casein kinase II (CKII). In vitro kinase assays showed CKII phosphorylates wild-type but not S284A mutant StarD10. Cells expressing S284A showed increased lipid transfer activity compared to wild-type, and purified recombinant StarD10 phosphorylated by CKII also had reduced transfer activity, indicating that Ser284 phosphorylation negatively regulates StarD10 lipid transfer activity and modulates its association with cellular membranes.","method":"Tandem mass spectrometry (phosphosite identification), in vitro CKII kinase assay with S284A mutant, lipid transfer assay in cell hypotonic extracts, lipid transfer assay with purified recombinant protein","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro kinase assay plus active-site mutagenesis plus functional lipid transfer assay, multiple orthogonal methods in one rigorous study","pmids":["17561512"],"is_preprint":false},{"year":2012,"finding":"Stard10 knockout mice show altered bile acid homeostasis: biliary secretion of bile acids and taurine-conjugated bile acids were elevated, secondary bile acid levels were reduced, ASBT expression was markedly lower in gallbladder and small intestine, and fecal bile acid excretion was increased. Mechanistically, PPARα-dependent genes regulating bile acid metabolism were downregulated in Stard10−/− liver, and loss of STARD10 impaired PPARα activity and expression of the PPARα target gene Cyp8b1 in mouse hepatoma cells. Biliary phosphatidylcholine secretion was not altered.","method":"Stard10 knockout mouse model, bile acid measurement, ASBT expression analysis, PPARα target gene expression, hepatoma cell functional assays","journal":"Biochimica et biophysica acta","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — knockout mouse with defined molecular phenotype in multiple tissues, single lab","pmids":["23200860"],"is_preprint":false},{"year":2015,"finding":"LPCAT1 directly interacts with StarD10 in alveolar type II cells. The interaction requires amino acids 79–271 of LPCAT1 and the START domain of StarD10. StarD10 knockdown significantly reduced phospholipid transport to lamellar bodies, indicating StarD10 is required for surfactant phospholipid trafficking from the ER to lamellar bodies. LPCAT1 did not interact with StarD2/PCTP.","method":"Co-immunoprecipitation, direct binding assay with domain-mapped constructs, siRNA knockdown with phospholipid trafficking assay to lamellar bodies","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — direct interaction demonstrated with domain mapping, functional knockdown confirming physiological role, single lab with multiple orthogonal methods","pmids":["26048993"],"is_preprint":false},{"year":2017,"finding":"β-cell-selective deletion of StarD10 in mice led to impaired glucose-stimulated Ca2+ dynamics and insulin secretion, and recapitulated the pattern of improved proinsulin processing (decreased proinsulin:insulin ratio) observed at the human GWAS signal. Overexpression of StarD10 in adult β cells improved glucose tolerance in high-fat-fed animals. Manipulation of Arap1 in β cells had no impact on insulin secretion or proinsulin conversion, placing STARD10 (not ARAP1) as the causal gene at this T2D locus.","method":"β-cell-selective Stard10 knockout mouse, glucose-stimulated insulin secretion assay, Ca2+ dynamics imaging, proinsulin:insulin ratio measurement, StarD10 overexpression in adult β cells, Arap1 β-cell manipulation as negative control","journal":"American journal of human genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional KO and OE in mice with defined molecular phenotypes, epistasis with ARAP1 negative control, convergent human and murine data","pmids":["28132686"],"is_preprint":false},{"year":2020,"finding":"X-ray crystallography of STARD10 to 2.3 Å resolution revealed a binding pocket capable of accommodating polyphosphoinositides; molecular docking and lipid overlay assays confirmed STARD10 binds inositides phosphorylated at the 3' position. β-cell-specific Stard10 KO islets showed altered phosphatidylinositol levels by lipidomics, dramatically increased 'rod-like' dense core granules by electron microscopy, and increased basal proinsulin secretion. Proteomic analysis identified the inositol lipid kinase PIP4K2C as a STARD10 binding partner.","method":"X-ray crystallography (2.3 Å), molecular docking, lipid overlay assay, lipidomics of KO islets, electron microscopy, pulse-chase secretion assay, co-immunoprecipitation/mass spectrometry proteomics","journal":"Molecular metabolism","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure plus lipid binding validation plus functional KO phenotype plus proteomic binding partner identification, multiple orthogonal methods in one study","pmids":["32416313"],"is_preprint":false},{"year":2021,"finding":"CRISPR-Cas9-mediated loss of STARD10 in human EndoC-βH1 cells impairs regulated glucose-stimulated insulin secretion, confirming a direct role for STARD10 in β-cell secretory function independent of ARAP1.","method":"CRISPR-Cas9 deletion in human EndoC-βH1 cells, glucose-stimulated insulin secretion assay","journal":"Cell reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — CRISPR KO in human β-cell line with defined secretory phenotype, single lab","pmids":["33535042"],"is_preprint":false},{"year":2019,"finding":"ERBB2 overexpression increases STARD10 expression, and ERBB2 downstream transcription factors p65, c-MYC, c-FOS, and c-JUN induce STARD10 promoter activity. Ethanol induces STARD10 and ERBB2 co-expression in vitro and in vivo; STARD10-mediated membrane fluidity and intracellular calcium changes impact ERBB2 signaling, including p65 nuclear translocation and binding to both ERBB2 and STARD10 promoters.","method":"Promoter activity assay, Western blotting, siRNA knockdown, overexpression in transfected breast cancer cells, calcium assay, membrane fluidity assay, ChIP-like p65 binding assessment","journal":"Journal of experimental & clinical cancer research : CR","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — promoter assays and functional assays in cell lines, single lab, multiple complementary methods but no reconstitution or structural validation","pmids":["30611309"],"is_preprint":false},{"year":2026,"finding":"In steatotic liver ischemia-reperfusion injury, hepatocyte-specific STARD10 knockout suppresses ferroptosis. Mechanistically, loss of STARD10 promotes nuclear translocation of YBX1, which binds to the ACSL1 promoter and transcriptionally represses ACSL1, leading to decreased polyunsaturated fatty acid-containing sphingolipids and attenuated lipid peroxidation. ACSL1 overexpression abolishes the protective effects of STARD10 KO, confirming STARD10 acts upstream of the YBX1–ACSL1 ferroptosis axis.","method":"AAV8-mediated hepatocyte-specific KO and OE, CRISPR/Cas9, co-immunoprecipitation/mass spectrometry, lipidomics, transcriptomics, ChIP-like YBX1 promoter binding assay, histopathology, ACSL1 rescue experiment","journal":"International journal of biological sciences","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — hepatocyte-specific KO/OE with defined ferroptosis phenotype and epistasis rescue, single lab, multiple omics methods","pmids":["41943848"],"is_preprint":false},{"year":2026,"finding":"STARD10 deletion in human embryonic stem cell-derived β-like cells reduced formation of INS+ β-like cells and proliferation. STARD10-null β-like cells showed higher triglyceride levels, reduced expression of ETFB (fatty acid β-oxidation), and impaired glycolytic function, mitochondrial oxidative phosphorylation, and palmitate oxidation.","method":"STARD10 deletion in human ESCs, directed β-cell differentiation, lipidomics, RNA-seq, Seahorse metabolic assay, flow cytometry for INS+ cells","journal":"Stem cell reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function in human stem cell model with defined metabolic and differentiation phenotypes, single lab","pmids":["41687621"],"is_preprint":false}],"current_model":"STARD10 is a phospholipid transfer protein with a START domain that selectively binds and shuttles phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositols (especially 3'-phosphorylated inositides) between membranes; its lipid transfer activity is negatively regulated by casein kinase II-mediated phosphorylation at Ser284; in pancreatic β-cells it controls insulin secretory granule biogenesis, proinsulin processing, and glucose-stimulated insulin secretion by modulating membrane phosphoinositide composition and interacting with PIP4K2C; in the liver it regulates bile acid homeostasis through PPARα signaling and, under steatotic conditions, drives ferroptosis via a YBX1–ACSL1 axis; it directly interacts with LPCAT1 to facilitate surfactant phospholipid trafficking to lamellar bodies in alveolar type II cells; and it cooperates with ErbB receptor signaling in cellular transformation."},"narrative":{"mechanistic_narrative":"STARD10 is a START-domain phospholipid transfer protein that selectively binds and shuttles phosphatidylcholine and phosphatidylethanolamine between membranes, with a preference for species bearing a saturated sn-1 and unsaturated sn-2 acyl chain, distinguishing it from related START proteins [PMID:15911624]. Crystallographic and lipid-binding analysis showed its pocket also accommodates polyphosphoinositides phosphorylated at the 3' position, linking its activity to cellular phosphoinositide composition [PMID:32416313]. Its transfer activity is negatively regulated by casein kinase II phosphorylation at Ser284, which reduces lipid transfer and modulates membrane association [PMID:17561512]. In pancreatic β-cells, STARD10 controls glucose-stimulated insulin secretion, Ca2+ dynamics, dense-core granule morphology, and proinsulin processing, establishing it as the causal gene at a type 2 diabetes GWAS locus over the neighboring ARAP1 [PMID:28132686, PMID:33535042]; it binds the inositol lipid kinase PIP4K2C, tying its function to phosphoinositide metabolism in the secretory pathway [PMID:32416313]. Beyond β-cells, STARD10 directly interacts with LPCAT1 via its START domain to traffic surfactant phospholipids from the ER to lamellar bodies in alveolar type II cells [PMID:26048993], regulates hepatic bile acid homeostasis through PPARα signaling [PMID:23200860], and in steatotic liver drives ferroptosis upstream of a YBX1–ACSL1 axis [PMID:41943848]. STARD10 is overexpressed in ErbB2-positive breast tumors and cooperates with ErbB receptor signaling to promote anchorage-independent growth [PMID:15150109, PMID:30611309].","teleology":[{"year":2004,"claim":"Established the first functional link for STARD10 to disease, showing it is a phosphoprotein overexpressed in ErbB2-positive tumors that cooperates with ErbB signaling in transformation.","evidence":"Soft agar anchorage-independent growth assay with StarD10/EGFR co-expression in murine fibroblasts and biochemical purification","pmids":["15150109"],"confidence":"Medium","gaps":["Molecular mechanism connecting lipid transfer to transformation not defined","Phosphorylation site not mapped in this work"]},{"year":2005,"claim":"Defined the core biochemical activity, demonstrating STARD10 is a selective PC/PE transfer protein distinct from other START proteins.","evidence":"ESR, FRET lipid binding, radiolabeled vesicle extraction, mass spectrometry, and in-cell photoactivatable lipid cross-linking","pmids":["15911624"],"confidence":"High","gaps":["Physiological membranes/organelles served not identified","Phosphoinositide binding not yet recognized"]},{"year":2005,"claim":"Identified STARD10 as a phosphoprotein and mapped an initial phosphorylation site, raising the question of regulated activity.","evidence":"Immunoaffinity purification, IMAC phosphopeptide enrichment, and tandem MS of Flag-tagged protein from HEK-293T","pmids":["15704244"],"confidence":"Medium","gaps":["No functional consequence of the identified site tested","Responsible kinase not identified"]},{"year":2007,"claim":"Showed lipid transfer is regulated post-translationally, identifying CKII phosphorylation at Ser284 as a negative switch on STARD10 activity.","evidence":"In vitro CKII kinase assay with S284A mutant plus lipid transfer assays using cell extracts and purified recombinant protein","pmids":["17561512"],"confidence":"High","gaps":["Upstream signals controlling CKII action on STARD10 unknown","Membrane association mechanism not structurally defined"]},{"year":2012,"claim":"Revealed a physiological role in the liver, linking STARD10 loss to disrupted bile acid homeostasis via impaired PPARα signaling.","evidence":"Stard10 knockout mice with bile acid measurement, ASBT and PPARα target gene analysis, and hepatoma cell assays","pmids":["23200860"],"confidence":"Medium","gaps":["Direct biochemical link between lipid transfer and PPARα activity not established","Single lab, single model"]},{"year":2015,"claim":"Connected STARD10 lipid transfer to a defined trafficking pathway by showing direct START-domain interaction with LPCAT1 enables surfactant phospholipid delivery to lamellar bodies.","evidence":"Co-IP, domain-mapped direct binding assays, and siRNA knockdown with lamellar body phospholipid trafficking assay in alveolar type II cells","pmids":["26048993"],"confidence":"High","gaps":["Whether transfer activity vs scaffolding drives trafficking unresolved","Regulation of the interaction not defined"]},{"year":2017,"claim":"Resolved which gene at a T2D GWAS locus is causal, establishing STARD10 (not ARAP1) as a controller of β-cell insulin secretion and proinsulin processing.","evidence":"β-cell-selective Stard10 KO and overexpression mice with GSIS, Ca2+ imaging, proinsulin:insulin ratio, and Arap1 negative control","pmids":["28132686"],"confidence":"High","gaps":["Molecular mechanism linking lipid handling to granule biogenesis not yet defined","Human cell confirmation pending at this stage"]},{"year":2020,"claim":"Provided the structural and lipidomic basis for β-cell function, showing STARD10 binds 3'-phosphoinositides and partners with PIP4K2C to shape granule biology.","evidence":"2.3 Å crystal structure, molecular docking, lipid overlay, KO islet lipidomics and electron microscopy, secretion assays, and Co-IP/MS proteomics","pmids":["32416313"],"confidence":"High","gaps":["Functional consequence of PIP4K2C binding not mechanistically dissected","How phosphoinositide handling alters granule morphology unresolved"]},{"year":2021,"claim":"Confirmed the β-cell secretory role in a human system, removing ambiguity about species- or model-specific effects.","evidence":"CRISPR-Cas9 deletion in human EndoC-βH1 cells with glucose-stimulated insulin secretion assay","pmids":["33535042"],"confidence":"Medium","gaps":["Single human cell line","Upstream lipid mechanism not re-tested here"]},{"year":2019,"claim":"Detailed how ErbB2 signaling and STARD10 reinforce each other transcriptionally, with STARD10 feeding back through membrane fluidity and calcium to ErbB2 signaling.","evidence":"Promoter activity assays, knockdown/overexpression in breast cancer cells, calcium and membrane fluidity assays, and p65 promoter-binding assessment","pmids":["30611309"],"confidence":"Medium","gaps":["Direct biochemical role of lipid transfer in the feedback loop unproven","In vivo tumor relevance not established"]},{"year":2026,"claim":"Identified a pro-ferroptotic function in steatotic liver, placing STARD10 upstream of a YBX1–ACSL1 transcriptional axis controlling lipid peroxidation.","evidence":"Hepatocyte-specific AAV8 KO/OE, CRISPR, Co-IP/MS, lipidomics, transcriptomics, YBX1 promoter binding, and ACSL1 rescue experiment","pmids":["41943848"],"confidence":"Medium","gaps":["How STARD10 controls YBX1 nuclear translocation mechanistically unclear","Single lab, single injury model"]},{"year":2026,"claim":"Extended β-cell relevance to human development and metabolism, showing STARD10 supports β-like cell formation and lipid oxidation capacity.","evidence":"STARD10 deletion in human ESC-derived β-like cells with lipidomics, RNA-seq, Seahorse metabolic assays, and flow cytometry","pmids":["41687621"],"confidence":"Medium","gaps":["Causal link between lipid transfer and differentiation defect not established","Mechanism of metabolic impairment not pinpointed"]},{"year":null,"claim":"How STARD10's single biochemical activity—regulated phospholipid/phosphoinositide transfer—mechanistically produces its tissue-specific roles across β-cell secretion, surfactant trafficking, bile acid metabolism, ferroptosis, and ErbB-driven transformation remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unified model linking lipid transfer to downstream transcriptional axes (PPARα, YBX1-ACSL1)","Membrane contact sites and donor/acceptor compartments in vivo undefined","Regulation of partner selection (LPCAT1 vs PIP4K2C) across tissues unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008289","term_label":"lipid binding","supporting_discovery_ids":[0,3,7]},{"term_id":"GO:0140104","term_label":"molecular carrier activity","supporting_discovery_ids":[0,5]}],"localization":[{"term_id":"GO:0005783","term_label":"endoplasmic reticulum","supporting_discovery_ids":[5]},{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[3,9]}],"pathway":[{"term_id":"R-HSA-1430728","term_label":"Metabolism","supporting_discovery_ids":[4,11]},{"term_id":"R-HSA-5357801","term_label":"Programmed Cell Death","supporting_discovery_ids":[10]}],"complexes":[],"partners":["LPCAT1","PIP4K2C","ERBB2"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9Y365","full_name":"START domain-containing protein 10","aliases":["Antigen NY-CO-28","PCTP-like protein","PCTP-L","Serologically defined colon cancer antigen 28","StAR-related lipid transfer protein 10"],"length_aa":291,"mass_kda":33.0,"function":"May play metabolic roles in sperm maturation or fertilization (By similarity). Phospholipid transfer protein that preferentially selects lipid species containing a palmitoyl or stearoyl chain on the sn-1 and an unsaturated fatty acyl chain (18:1 or 18:2) on the sn-2 position. Able to transfer phosphatidylcholine (PC) and phosphatidyetanolamline (PE) between membranes","subcellular_location":"Cell projection, cilium, flagellum; Cytoplasm; Membrane","url":"https://www.uniprot.org/uniprotkb/Q9Y365/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/STARD10","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":[],"url":"https://opencell.sf.czbiohub.org/search/STARD10","total_profiled":1310},"omim":[{"mim_id":"617382","title":"START DOMAIN-CONTAINING PROTEIN 10; STARD10","url":"https://www.omim.org/entry/617382"},{"mim_id":"125853","title":"TYPE 2 DIABETES MELLITUS; T2D","url":"https://www.omim.org/entry/125853"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Cytosol","reliability":"Supported"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"liver","ntpm":710.4}],"url":"https://www.proteinatlas.org/search/STARD10"},"hgnc":{"alias_symbol":["NY-CO-28","CGI-52","PCTP2"],"prev_symbol":["SDCCAG28"]},"alphafold":{"accession":"Q9Y365","domains":[{"cath_id":"3.30.530.20","chopping":"26-230_240-267","consensus_level":"high","plddt":93.7264,"start":26,"end":267}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9Y365","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9Y365-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9Y365-F1-predicted_aligned_error_v6.png","plddt_mean":86.94},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=STARD10","jax_strain_url":"https://www.jax.org/strain/search?query=STARD10"},"sequence":{"accession":"Q9Y365","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9Y365.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9Y365/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9Y365"}},"corpus_meta":[{"pmid":"20543867","id":"PMC_20543867","title":"miR-661 expression in SNAI1-induced epithelial to mesenchymal transition contributes to breast cancer cell invasion by targeting Nectin-1 and StarD10 messengers.","date":"2010","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/20543867","citation_count":107,"is_preprint":false},{"pmid":"15911624","id":"PMC_15911624","title":"StarD10, a START domain protein overexpressed in breast cancer, functions as a phospholipid transfer protein.","date":"2005","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/15911624","citation_count":74,"is_preprint":false},{"pmid":"28132686","id":"PMC_28132686","title":"Decreased STARD10 Expression Is Associated with Defective Insulin Secretion in Humans and Mice.","date":"2017","source":"American journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/28132686","citation_count":52,"is_preprint":false},{"pmid":"15150109","id":"PMC_15150109","title":"The phosphoprotein StarD10 is overexpressed in breast cancer and cooperates with ErbB receptors in cellular transformation.","date":"2004","source":"Cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/15150109","citation_count":35,"is_preprint":false},{"pmid":"32416313","id":"PMC_32416313","title":"The type 2 diabetes gene product STARD10 is a phosphoinositide-binding protein that controls insulin secretory granule biogenesis.","date":"2020","source":"Molecular metabolism","url":"https://pubmed.ncbi.nlm.nih.gov/32416313","citation_count":23,"is_preprint":false},{"pmid":"28412359","id":"PMC_28412359","title":"Potentiation of docetaxel sensitivity by miR-638 via regulation of STARD10 pathway in human breast cancer cells.","date":"2017","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/28412359","citation_count":22,"is_preprint":false},{"pmid":"26048993","id":"PMC_26048993","title":"Lysophosphatidylcholine Acyltransferase 1 (LPCAT1) Specifically Interacts with Phospholipid Transfer Protein StarD10 to Facilitate Surfactant Phospholipid Trafficking in Alveolar Type II Cells.","date":"2015","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/26048993","citation_count":20,"is_preprint":false},{"pmid":"23200860","id":"PMC_23200860","title":"Disruption of Stard10 gene alters the PPARα-mediated bile acid homeostasis.","date":"2012","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/23200860","citation_count":17,"is_preprint":false},{"pmid":"17561512","id":"PMC_17561512","title":"Phosphorylation of StarD10 on serine 284 by casein kinase II modulates its lipid transfer activity.","date":"2007","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/17561512","citation_count":12,"is_preprint":false},{"pmid":"30611309","id":"PMC_30611309","title":"Star-related lipid transfer protein 10 (STARD10): a novel key player in alcohol-induced breast cancer progression.","date":"2019","source":"Journal of experimental & clinical cancer research : CR","url":"https://pubmed.ncbi.nlm.nih.gov/30611309","citation_count":12,"is_preprint":false},{"pmid":"33535042","id":"PMC_33535042","title":"Chromatin 3D interaction analysis of the STARD10 locus unveils FCHSD2 as a regulator of insulin secretion.","date":"2021","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/33535042","citation_count":8,"is_preprint":false},{"pmid":"15704244","id":"PMC_15704244","title":"Breast cancer protein StarD10 identified by three-dimensional separation using free-flow electrophoresis, reversed-phase high-performance liquid chromatography, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis.","date":"2005","source":"Electrophoresis","url":"https://pubmed.ncbi.nlm.nih.gov/15704244","citation_count":7,"is_preprint":false},{"pmid":"41687621","id":"PMC_41687621","title":"STARD10 regulates human pancreatic β cell differentiation and triglyceride metabolism.","date":"2026","source":"Stem cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/41687621","citation_count":0,"is_preprint":false},{"pmid":"41943848","id":"PMC_41943848","title":"Targeting STARD10 Alleviates Steatotic Liver Injury by Suppressing YBX1/ACSL1-Mediated Ferroptosis.","date":"2026","source":"International journal of biological sciences","url":"https://pubmed.ncbi.nlm.nih.gov/41943848","citation_count":0,"is_preprint":false},{"pmid":"32667144","id":"PMC_32667144","title":"Retraction: miR-661 expression in SNAI1-induced epithelial to mesenchymal transition contributes to breast cancer cell invasion by targeting Nectin-1 and StarD10 messengers.","date":"2015","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/32667144","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":9885,"output_tokens":3580,"usd":0.041677,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":11347,"output_tokens":3860,"usd":0.076618,"stage2_stop_reason":"end_turn"},"total_usd":0.118295,"stage1_batch_id":"msgbatch_013LWZZT6MWaqB9qyTSeQBmU","stage2_batch_id":"msgbatch_0194ZzQaTGNpruoNJBbEMbt3","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2005,\n      \"finding\": \"StarD10 functions as a phospholipid transfer protein, selectively binding and transferring phosphatidylcholine (PC) and phosphatidylethanolamine (PE) between membranes. Binding specificity was demonstrated by ESR, FRET-based assays, and selective extraction from radiolabeled vesicles. Mass spectrometry revealed preference for lipid species with palmitoyl/stearoyl at sn-1 and unsaturated fatty acyl chain at sn-2. In vivo lipid binding was confirmed by photoactivatable PC cross-linking in HEK-293T cells. This distinguishes StarD10 from related START domain proteins Pctp and CERT.\",\n      \"method\": \"Electron spin resonance, FRET-based lipid binding assay, radiolabeled lipid extraction, mass spectrometry, photoactivatable lipid cross-linking in transfected cells\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — multiple orthogonal in vitro biochemical assays plus in vivo cross-linking, single rigorous study\",\n      \"pmids\": [\"15911624\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"StarD10 is a phosphoprotein overexpressed in ErbB2-positive breast tumors; coexpression of StarD10 with ErbB1/EGFR in murine fibroblasts enhanced anchorage-independent growth in soft agar, demonstrating functional cooperation between StarD10 and ErbB receptor signaling.\",\n      \"method\": \"Soft agar anchorage-independent growth assay, co-expression in murine fibroblasts, biochemical purification and phosphoserine antibody cross-reactivity\",\n      \"journal\": \"Cancer research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — defined cellular phenotype by loss/gain-of-function in a relevant assay, single lab but multiple methods\",\n      \"pmids\": [\"15150109\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"StarD10 was identified as a phosphoprotein; a phosphorylation site at Ser-259 was identified by tandem mass spectrometry of immunoaffinity-purified Flag-tagged StarD10 from HEK-293T cells.\",\n      \"method\": \"Immunoaffinity purification, IMAC enrichment of phosphopeptides, tandem mass spectrometry\",\n      \"journal\": \"Electrophoresis\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — single lab, single method (MS-based phosphosite identification), no functional validation of this specific site in this paper\",\n      \"pmids\": [\"15704244\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"StarD10 is phosphorylated in vivo at serine 284 by casein kinase II (CKII). In vitro kinase assays showed CKII phosphorylates wild-type but not S284A mutant StarD10. Cells expressing S284A showed increased lipid transfer activity compared to wild-type, and purified recombinant StarD10 phosphorylated by CKII also had reduced transfer activity, indicating that Ser284 phosphorylation negatively regulates StarD10 lipid transfer activity and modulates its association with cellular membranes.\",\n      \"method\": \"Tandem mass spectrometry (phosphosite identification), in vitro CKII kinase assay with S284A mutant, lipid transfer assay in cell hypotonic extracts, lipid transfer assay with purified recombinant protein\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro kinase assay plus active-site mutagenesis plus functional lipid transfer assay, multiple orthogonal methods in one rigorous study\",\n      \"pmids\": [\"17561512\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Stard10 knockout mice show altered bile acid homeostasis: biliary secretion of bile acids and taurine-conjugated bile acids were elevated, secondary bile acid levels were reduced, ASBT expression was markedly lower in gallbladder and small intestine, and fecal bile acid excretion was increased. Mechanistically, PPARα-dependent genes regulating bile acid metabolism were downregulated in Stard10−/− liver, and loss of STARD10 impaired PPARα activity and expression of the PPARα target gene Cyp8b1 in mouse hepatoma cells. Biliary phosphatidylcholine secretion was not altered.\",\n      \"method\": \"Stard10 knockout mouse model, bile acid measurement, ASBT expression analysis, PPARα target gene expression, hepatoma cell functional assays\",\n      \"journal\": \"Biochimica et biophysica acta\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — knockout mouse with defined molecular phenotype in multiple tissues, single lab\",\n      \"pmids\": [\"23200860\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"LPCAT1 directly interacts with StarD10 in alveolar type II cells. The interaction requires amino acids 79–271 of LPCAT1 and the START domain of StarD10. StarD10 knockdown significantly reduced phospholipid transport to lamellar bodies, indicating StarD10 is required for surfactant phospholipid trafficking from the ER to lamellar bodies. LPCAT1 did not interact with StarD2/PCTP.\",\n      \"method\": \"Co-immunoprecipitation, direct binding assay with domain-mapped constructs, siRNA knockdown with phospholipid trafficking assay to lamellar bodies\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — direct interaction demonstrated with domain mapping, functional knockdown confirming physiological role, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"26048993\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"β-cell-selective deletion of StarD10 in mice led to impaired glucose-stimulated Ca2+ dynamics and insulin secretion, and recapitulated the pattern of improved proinsulin processing (decreased proinsulin:insulin ratio) observed at the human GWAS signal. Overexpression of StarD10 in adult β cells improved glucose tolerance in high-fat-fed animals. Manipulation of Arap1 in β cells had no impact on insulin secretion or proinsulin conversion, placing STARD10 (not ARAP1) as the causal gene at this T2D locus.\",\n      \"method\": \"β-cell-selective Stard10 knockout mouse, glucose-stimulated insulin secretion assay, Ca2+ dynamics imaging, proinsulin:insulin ratio measurement, StarD10 overexpression in adult β cells, Arap1 β-cell manipulation as negative control\",\n      \"journal\": \"American journal of human genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional KO and OE in mice with defined molecular phenotypes, epistasis with ARAP1 negative control, convergent human and murine data\",\n      \"pmids\": [\"28132686\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"X-ray crystallography of STARD10 to 2.3 Å resolution revealed a binding pocket capable of accommodating polyphosphoinositides; molecular docking and lipid overlay assays confirmed STARD10 binds inositides phosphorylated at the 3' position. β-cell-specific Stard10 KO islets showed altered phosphatidylinositol levels by lipidomics, dramatically increased 'rod-like' dense core granules by electron microscopy, and increased basal proinsulin secretion. Proteomic analysis identified the inositol lipid kinase PIP4K2C as a STARD10 binding partner.\",\n      \"method\": \"X-ray crystallography (2.3 Å), molecular docking, lipid overlay assay, lipidomics of KO islets, electron microscopy, pulse-chase secretion assay, co-immunoprecipitation/mass spectrometry proteomics\",\n      \"journal\": \"Molecular metabolism\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure plus lipid binding validation plus functional KO phenotype plus proteomic binding partner identification, multiple orthogonal methods in one study\",\n      \"pmids\": [\"32416313\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"CRISPR-Cas9-mediated loss of STARD10 in human EndoC-βH1 cells impairs regulated glucose-stimulated insulin secretion, confirming a direct role for STARD10 in β-cell secretory function independent of ARAP1.\",\n      \"method\": \"CRISPR-Cas9 deletion in human EndoC-βH1 cells, glucose-stimulated insulin secretion assay\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — CRISPR KO in human β-cell line with defined secretory phenotype, single lab\",\n      \"pmids\": [\"33535042\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"ERBB2 overexpression increases STARD10 expression, and ERBB2 downstream transcription factors p65, c-MYC, c-FOS, and c-JUN induce STARD10 promoter activity. Ethanol induces STARD10 and ERBB2 co-expression in vitro and in vivo; STARD10-mediated membrane fluidity and intracellular calcium changes impact ERBB2 signaling, including p65 nuclear translocation and binding to both ERBB2 and STARD10 promoters.\",\n      \"method\": \"Promoter activity assay, Western blotting, siRNA knockdown, overexpression in transfected breast cancer cells, calcium assay, membrane fluidity assay, ChIP-like p65 binding assessment\",\n      \"journal\": \"Journal of experimental & clinical cancer research : CR\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — promoter assays and functional assays in cell lines, single lab, multiple complementary methods but no reconstitution or structural validation\",\n      \"pmids\": [\"30611309\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"In steatotic liver ischemia-reperfusion injury, hepatocyte-specific STARD10 knockout suppresses ferroptosis. Mechanistically, loss of STARD10 promotes nuclear translocation of YBX1, which binds to the ACSL1 promoter and transcriptionally represses ACSL1, leading to decreased polyunsaturated fatty acid-containing sphingolipids and attenuated lipid peroxidation. ACSL1 overexpression abolishes the protective effects of STARD10 KO, confirming STARD10 acts upstream of the YBX1–ACSL1 ferroptosis axis.\",\n      \"method\": \"AAV8-mediated hepatocyte-specific KO and OE, CRISPR/Cas9, co-immunoprecipitation/mass spectrometry, lipidomics, transcriptomics, ChIP-like YBX1 promoter binding assay, histopathology, ACSL1 rescue experiment\",\n      \"journal\": \"International journal of biological sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — hepatocyte-specific KO/OE with defined ferroptosis phenotype and epistasis rescue, single lab, multiple omics methods\",\n      \"pmids\": [\"41943848\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"STARD10 deletion in human embryonic stem cell-derived β-like cells reduced formation of INS+ β-like cells and proliferation. STARD10-null β-like cells showed higher triglyceride levels, reduced expression of ETFB (fatty acid β-oxidation), and impaired glycolytic function, mitochondrial oxidative phosphorylation, and palmitate oxidation.\",\n      \"method\": \"STARD10 deletion in human ESCs, directed β-cell differentiation, lipidomics, RNA-seq, Seahorse metabolic assay, flow cytometry for INS+ cells\",\n      \"journal\": \"Stem cell reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function in human stem cell model with defined metabolic and differentiation phenotypes, single lab\",\n      \"pmids\": [\"41687621\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"STARD10 is a phospholipid transfer protein with a START domain that selectively binds and shuttles phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositols (especially 3'-phosphorylated inositides) between membranes; its lipid transfer activity is negatively regulated by casein kinase II-mediated phosphorylation at Ser284; in pancreatic β-cells it controls insulin secretory granule biogenesis, proinsulin processing, and glucose-stimulated insulin secretion by modulating membrane phosphoinositide composition and interacting with PIP4K2C; in the liver it regulates bile acid homeostasis through PPARα signaling and, under steatotic conditions, drives ferroptosis via a YBX1–ACSL1 axis; it directly interacts with LPCAT1 to facilitate surfactant phospholipid trafficking to lamellar bodies in alveolar type II cells; and it cooperates with ErbB receptor signaling in cellular transformation.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"STARD10 is a START-domain phospholipid transfer protein that selectively binds and shuttles phosphatidylcholine and phosphatidylethanolamine between membranes, with a preference for species bearing a saturated sn-1 and unsaturated sn-2 acyl chain, distinguishing it from related START proteins [#0]. Crystallographic and lipid-binding analysis showed its pocket also accommodates polyphosphoinositides phosphorylated at the 3' position, linking its activity to cellular phosphoinositide composition [#7]. Its transfer activity is negatively regulated by casein kinase II phosphorylation at Ser284, which reduces lipid transfer and modulates membrane association [#3]. In pancreatic \\u03b2-cells, STARD10 controls glucose-stimulated insulin secretion, Ca2+ dynamics, dense-core granule morphology, and proinsulin processing, establishing it as the causal gene at a type 2 diabetes GWAS locus over the neighboring ARAP1 [#6, #8]; it binds the inositol lipid kinase PIP4K2C, tying its function to phosphoinositide metabolism in the secretory pathway [#7]. Beyond \\u03b2-cells, STARD10 directly interacts with LPCAT1 via its START domain to traffic surfactant phospholipids from the ER to lamellar bodies in alveolar type II cells [#5], regulates hepatic bile acid homeostasis through PPAR\\u03b1 signaling [#4], and in steatotic liver drives ferroptosis upstream of a YBX1\\u2013ACSL1 axis [#10]. STARD10 is overexpressed in ErbB2-positive breast tumors and cooperates with ErbB receptor signaling to promote anchorage-independent growth [#1, #9].\",\n  \"teleology\": [\n    {\n      \"year\": 2004,\n      \"claim\": \"Established the first functional link for STARD10 to disease, showing it is a phosphoprotein overexpressed in ErbB2-positive tumors that cooperates with ErbB signaling in transformation.\",\n      \"evidence\": \"Soft agar anchorage-independent growth assay with StarD10/EGFR co-expression in murine fibroblasts and biochemical purification\",\n      \"pmids\": [\"15150109\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular mechanism connecting lipid transfer to transformation not defined\", \"Phosphorylation site not mapped in this work\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Defined the core biochemical activity, demonstrating STARD10 is a selective PC/PE transfer protein distinct from other START proteins.\",\n      \"evidence\": \"ESR, FRET lipid binding, radiolabeled vesicle extraction, mass spectrometry, and in-cell photoactivatable lipid cross-linking\",\n      \"pmids\": [\"15911624\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Physiological membranes/organelles served not identified\", \"Phosphoinositide binding not yet recognized\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Identified STARD10 as a phosphoprotein and mapped an initial phosphorylation site, raising the question of regulated activity.\",\n      \"evidence\": \"Immunoaffinity purification, IMAC phosphopeptide enrichment, and tandem MS of Flag-tagged protein from HEK-293T\",\n      \"pmids\": [\"15704244\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No functional consequence of the identified site tested\", \"Responsible kinase not identified\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Showed lipid transfer is regulated post-translationally, identifying CKII phosphorylation at Ser284 as a negative switch on STARD10 activity.\",\n      \"evidence\": \"In vitro CKII kinase assay with S284A mutant plus lipid transfer assays using cell extracts and purified recombinant protein\",\n      \"pmids\": [\"17561512\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Upstream signals controlling CKII action on STARD10 unknown\", \"Membrane association mechanism not structurally defined\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Revealed a physiological role in the liver, linking STARD10 loss to disrupted bile acid homeostasis via impaired PPAR\\u03b1 signaling.\",\n      \"evidence\": \"Stard10 knockout mice with bile acid measurement, ASBT and PPAR\\u03b1 target gene analysis, and hepatoma cell assays\",\n      \"pmids\": [\"23200860\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct biochemical link between lipid transfer and PPAR\\u03b1 activity not established\", \"Single lab, single model\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Connected STARD10 lipid transfer to a defined trafficking pathway by showing direct START-domain interaction with LPCAT1 enables surfactant phospholipid delivery to lamellar bodies.\",\n      \"evidence\": \"Co-IP, domain-mapped direct binding assays, and siRNA knockdown with lamellar body phospholipid trafficking assay in alveolar type II cells\",\n      \"pmids\": [\"26048993\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether transfer activity vs scaffolding drives trafficking unresolved\", \"Regulation of the interaction not defined\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Resolved which gene at a T2D GWAS locus is causal, establishing STARD10 (not ARAP1) as a controller of \\u03b2-cell insulin secretion and proinsulin processing.\",\n      \"evidence\": \"\\u03b2-cell-selective Stard10 KO and overexpression mice with GSIS, Ca2+ imaging, proinsulin:insulin ratio, and Arap1 negative control\",\n      \"pmids\": [\"28132686\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular mechanism linking lipid handling to granule biogenesis not yet defined\", \"Human cell confirmation pending at this stage\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Provided the structural and lipidomic basis for \\u03b2-cell function, showing STARD10 binds 3'-phosphoinositides and partners with PIP4K2C to shape granule biology.\",\n      \"evidence\": \"2.3 \\u00c5 crystal structure, molecular docking, lipid overlay, KO islet lipidomics and electron microscopy, secretion assays, and Co-IP/MS proteomics\",\n      \"pmids\": [\"32416313\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional consequence of PIP4K2C binding not mechanistically dissected\", \"How phosphoinositide handling alters granule morphology unresolved\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Confirmed the \\u03b2-cell secretory role in a human system, removing ambiguity about species- or model-specific effects.\",\n      \"evidence\": \"CRISPR-Cas9 deletion in human EndoC-\\u03b2H1 cells with glucose-stimulated insulin secretion assay\",\n      \"pmids\": [\"33535042\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single human cell line\", \"Upstream lipid mechanism not re-tested here\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Detailed how ErbB2 signaling and STARD10 reinforce each other transcriptionally, with STARD10 feeding back through membrane fluidity and calcium to ErbB2 signaling.\",\n      \"evidence\": \"Promoter activity assays, knockdown/overexpression in breast cancer cells, calcium and membrane fluidity assays, and p65 promoter-binding assessment\",\n      \"pmids\": [\"30611309\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct biochemical role of lipid transfer in the feedback loop unproven\", \"In vivo tumor relevance not established\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Identified a pro-ferroptotic function in steatotic liver, placing STARD10 upstream of a YBX1\\u2013ACSL1 transcriptional axis controlling lipid peroxidation.\",\n      \"evidence\": \"Hepatocyte-specific AAV8 KO/OE, CRISPR, Co-IP/MS, lipidomics, transcriptomics, YBX1 promoter binding, and ACSL1 rescue experiment\",\n      \"pmids\": [\"41943848\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"How STARD10 controls YBX1 nuclear translocation mechanistically unclear\", \"Single lab, single injury model\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Extended \\u03b2-cell relevance to human development and metabolism, showing STARD10 supports \\u03b2-like cell formation and lipid oxidation capacity.\",\n      \"evidence\": \"STARD10 deletion in human ESC-derived \\u03b2-like cells with lipidomics, RNA-seq, Seahorse metabolic assays, and flow cytometry\",\n      \"pmids\": [\"41687621\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Causal link between lipid transfer and differentiation defect not established\", \"Mechanism of metabolic impairment not pinpointed\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How STARD10's single biochemical activity\\u2014regulated phospholipid/phosphoinositide transfer\\u2014mechanistically produces its tissue-specific roles across \\u03b2-cell secretion, surfactant trafficking, bile acid metabolism, ferroptosis, and ErbB-driven transformation remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No unified model linking lipid transfer to downstream transcriptional axes (PPAR\\u03b1, YBX1-ACSL1)\", \"Membrane contact sites and donor/acceptor compartments in vivo undefined\", \"Regulation of partner selection (LPCAT1 vs PIP4K2C) across tissues unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008289\", \"supporting_discovery_ids\": [0, 3, 7]},\n      {\"term_id\": \"GO:0140104\", \"supporting_discovery_ids\": [0, 5]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005783\", \"supporting_discovery_ids\": [5]},\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [3, 9]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1430728\", \"supporting_discovery_ids\": [4, 11]},\n      {\"term_id\": \"R-HSA-5357801\", \"supporting_discovery_ids\": [10]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"LPCAT1\", \"PIP4K2C\", \"ERBB2\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}