{"gene":"ACBD4","run_date":"2026-06-09T22:02:38","timeline":{"discoveries":[{"year":2017,"finding":"ACBD4 is a tail-anchored peroxisomal membrane protein that interacts with the ER protein VAPB (vesicle-associated membrane protein-associated protein B) to promote peroxisome-ER membrane contact site associations.","method":"Molecular cell biology characterization of ACBD4 as tail-anchored peroxisomal membrane protein; interaction with VAPB demonstrated; overexpression/loss-of-function showing altered peroxisome-ER associations","journal":"Cell cycle (Georgetown, Tex.)","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal protein interaction data combined with localization experiments and functional consequence (altered peroxisome-ER contacts), replicated in subsequent independent studies","pmids":["28463579"],"is_preprint":false},{"year":2023,"finding":"Loss of ACBD4 does not reduce peroxisome-ER connections or result in accumulation of very long-chain fatty acids (VLCFAs); instead, loss of ACBD4 increases the rate of peroxisomal β-oxidation of VLCFAs, suggesting a regulatory rather than primary tethering role at the peroxisome-ER interface. Additionally, ACBD4 interacts with ACBD5 independently of VAPB binding.","method":"Loss-of-function (ACBD4 knockout in HEK293 cells) combined with molecular cell biology, biochemical assays, and lipidomics; co-immunoprecipitation for ACBD4-ACBD5 interaction","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (KO, lipidomics, Co-IP) in a single rigorous study establishing mechanistic distinction from ACBD5","pmids":["37414147"],"is_preprint":false},{"year":2019,"finding":"ACBD4 and ACBD5 function as peroxisomal tethering components that physically interact with ER-resident VAPB to form peroxisome-ER membrane contact sites; overexpression or loss of these tether proteins alters the extent of peroxisome-ER interactions and impacts lipid exchange between the two compartments.","method":"Proximity ligation assay and split superfolder GFP reporter system to monitor peroxisome-ER interactions; manipulation of tether protein levels with quantification of contact site changes","journal":"Contact (Thousand Oaks (Ventura County, Calif.))","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — two orthogonal fluorescence-based assays used to validate contact site tethering function, single lab but multiple methods","pmids":["31198905"],"is_preprint":false},{"year":2024,"finding":"The FFAT motif in ACBD4 mediates interaction with ER-resident VAP proteins to tether peroxisomes to the ER; this FFAT-VAP tethering function is conserved in Drosophila ACBD4/5-like protein (which has a functional FFAT motif tethering peroxisomes to the ER via Dm_Vap33), while the fungal Ustilago maydis ACBD4/5-like protein lacks a functional FFAT motif and does not interact with Um_Vap33.","method":"Phylogenetic analysis combined with experimental validation: FFAT motif functional assays, co-localization and interaction studies in Drosophila and fungal model organisms, depletion experiments showing peroxisome redistribution","journal":"Biochimica et biophysica acta. Molecular cell research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — combined phylogenetic and experimental approach across model organisms, multiple cell biology methods, but primarily in non-human model systems for the mechanistic validation","pmids":["39271061"],"is_preprint":false},{"year":2023,"finding":"ACBD4 (and its paralog ACBD5) bind ER membrane protein VAPB to mediate peroxisome-ER contacts; immunoprecipitation can be used to identify residues important for regulation of this interaction, including phosphorylation sites.","method":"Immunoprecipitation with antibody-conjugated beads followed by western blot analysis; domain deletion and mutagenesis to identify interaction determinants including phosphorylation","journal":"Methods in molecular biology (Clifton, N.J.)","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — immunoprecipitation-based interaction study with domain analysis, single lab, methods paper context","pmids":["36952197"],"is_preprint":false}],"current_model":"ACBD4 is a tail-anchored peroxisomal membrane protein that uses its FFAT motif to interact with ER-resident VAPB, forming peroxisome-ER membrane contact sites; while its paralog ACBD5 acts as the primary tether and VLCFA recruitment factor, ACBD4 plays a regulatory role in peroxisomal β-oxidation of very long-chain fatty acids and also interacts with ACBD5 independently of VAPB."},"narrative":{"mechanistic_narrative":"ACBD4 is a tail-anchored peroxisomal membrane protein that helps organize peroxisome-endoplasmic reticulum membrane contact sites and modulates peroxisomal lipid metabolism [PMID:28463579, PMID:37414147]. It uses an FFAT motif to bind the ER-resident protein VAPB, and overexpression or loss of ACBD4 alters the extent of peroxisome-ER associations [PMID:28463579, PMID:39271061]. This FFAT-VAP tethering function is evolutionarily conserved, being retained in the Drosophila ACBD4/5-like protein but lost in the fungal Ustilago maydis ortholog, which lacks a functional FFAT motif [PMID:39271061]. Functionally, ACBD4 plays a regulatory rather than primary tethering role: its loss does not reduce peroxisome-ER connections or cause very long-chain fatty acid accumulation but instead increases the rate of peroxisomal β-oxidation of VLCFAs, distinguishing it mechanistically from its paralog ACBD5 [PMID:37414147]. ACBD4 also interacts directly with ACBD5 independently of VAPB binding [PMID:37414147]. Beyond these contact-site and metabolic regulatory roles, no further mechanistic detail has been characterized in the available corpus.","teleology":[{"year":2017,"claim":"Established ACBD4 as a peroxisomal membrane protein and assigned it a role in inter-organelle contact, answering whether it physically links peroxisomes to another compartment.","evidence":"Characterization as a tail-anchored peroxisomal protein with demonstrated VAPB interaction and altered peroxisome-ER associations on manipulation","pmids":["28463579"],"confidence":"High","gaps":["Did not distinguish whether ACBD4 is a primary tether or a regulatory factor","No functional consequence for lipid metabolism established"]},{"year":2019,"claim":"Quantified the contact-site tethering activity of ACBD4 and linked peroxisome-ER contacts to lipid exchange, addressing the functional output of these junctions.","evidence":"Proximity ligation and split-superfolder-GFP reporter assays with tether-level manipulation","pmids":["31198905"],"confidence":"Medium","gaps":["Single-lab fluorescence assays","Did not separate ACBD4-specific from ACBD5-specific contributions"]},{"year":2023,"claim":"Distinguished ACBD4 from ACBD5 by showing ACBD4 loss does not impair tethering or cause VLCFA accumulation but accelerates β-oxidation, establishing a regulatory rather than tethering role and a VAPB-independent ACBD5 interaction.","evidence":"ACBD4 knockout in HEK293 cells with lipidomics, biochemical assays, and co-immunoprecipitation","pmids":["37414147"],"confidence":"High","gaps":["Molecular basis for accelerated β-oxidation upon ACBD4 loss unresolved","Functional consequence of ACBD4-ACBD5 interaction unknown"]},{"year":2023,"claim":"Identified interaction determinants, including phosphorylation sites, as candidate regulators of ACBD4-VAPB binding.","evidence":"Immunoprecipitation with domain deletion and mutagenesis (methods paper context)","pmids":["36952197"],"confidence":"Medium","gaps":["Functional impact of specific phosphorylation sites not demonstrated","Kinase and regulatory context unknown"]},{"year":2024,"claim":"Mapped the FFAT motif as the VAP-binding element and traced its evolutionary conservation, clarifying the structural basis and phylogenetic distribution of ACBD4-mediated tethering.","evidence":"Phylogenetic analysis with FFAT functional assays and interaction/depletion studies in Drosophila and Ustilago maydis","pmids":["39271061"],"confidence":"Medium","gaps":["Mechanistic validation primarily in non-human model organisms","Structural model of the FFAT-VAP interface not resolved"]},{"year":null,"claim":"How ACBD4 mechanistically restrains the rate of peroxisomal VLCFA β-oxidation, and how its VAPB-independent association with ACBD5 fits into contact-site assembly, remain unresolved.","evidence":"","pmids":[],"confidence":"High","gaps":["No molecular mechanism linking ACBD4 to β-oxidation rate control","Role of the ACBD4-ACBD5 complex undefined","No structural data on the contact-site assembly"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,2,3]}],"localization":[{"term_id":"GO:0005777","term_label":"peroxisome","supporting_discovery_ids":[0,1]},{"term_id":"GO:0005783","term_label":"endoplasmic reticulum","supporting_discovery_ids":[0,2]}],"pathway":[{"term_id":"R-HSA-1430728","term_label":"Metabolism","supporting_discovery_ids":[1]}],"complexes":["peroxisome-ER membrane contact site"],"partners":["VAPB","ACBD5"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q8NC06","full_name":"Acyl-CoA-binding domain-containing protein 4","aliases":[],"length_aa":268,"mass_kda":30.3,"function":"Binds medium- and long-chain acyl-CoA esters and may function as an intracellular carrier of acyl-CoA esters","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/Q8NC06/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/ACBD4","classification":"Not Classified","n_dependent_lines":5,"n_total_lines":1208,"dependency_fraction":0.0041390728476821195},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"LPCAT1","stoichiometry":0.2},{"gene":"VAPA","stoichiometry":0.2},{"gene":"VAPB","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/ACBD4","total_profiled":1310},"omim":[{"mim_id":"619968","title":"ACYL-CoA-BINDING DOMAIN-CONTAINING PROTEIN 4; ACBD4","url":"https://www.omim.org/entry/619968"},{"mim_id":"605704","title":"VAMP-ASSOCIATED PROTEIN B AND C; VAPB","url":"https://www.omim.org/entry/605704"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoplasm","reliability":"Approved"},{"location":"Vesicles","reliability":"Approved"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"liver","ntpm":90.7}],"url":"https://www.proteinatlas.org/search/ACBD4"},"hgnc":{"alias_symbol":["FLJ13322"],"prev_symbol":[]},"alphafold":{"accession":"Q8NC06","domains":[],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8NC06","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8NC06-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8NC06-F1-predicted_aligned_error_v6.png","plddt_mean":64.44},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=ACBD4","jax_strain_url":"https://www.jax.org/strain/search?query=ACBD4"},"sequence":{"accession":"Q8NC06","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8NC06.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8NC06/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8NC06"}},"corpus_meta":[{"pmid":"28463579","id":"PMC_28463579","title":"Peroxisomal ACBD4 interacts with VAPB and promotes ER-peroxisome associations.","date":"2017","source":"Cell cycle (Georgetown, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/28463579","citation_count":67,"is_preprint":false},{"pmid":"22817472","id":"PMC_22817472","title":"Brain transcriptome variation among behaviorally distinct strains of zebrafish (Danio rerio).","date":"2012","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/22817472","citation_count":41,"is_preprint":false},{"pmid":"23284922","id":"PMC_23284922","title":"Global effect of inauhzin on human p53-responsive transcriptome.","date":"2012","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/23284922","citation_count":20,"is_preprint":false},{"pmid":"30608189","id":"PMC_30608189","title":"Systems Genetics Approaches in Rat Identify Novel Genes and Gene Networks Associated With Cardiac Conduction.","date":"2018","source":"Journal of the American Heart Association","url":"https://pubmed.ncbi.nlm.nih.gov/30608189","citation_count":19,"is_preprint":false},{"pmid":"31198905","id":"PMC_31198905","title":"Fluorescent tools to analyse peroxisome-ER interactions in mammalian cells.","date":"2019","source":"Contact (Thousand Oaks (Ventura County, Calif.))","url":"https://pubmed.ncbi.nlm.nih.gov/31198905","citation_count":16,"is_preprint":false},{"pmid":"37414147","id":"PMC_37414147","title":"Differential roles for ACBD4 and ACBD5 in peroxisome-ER interactions and lipid metabolism.","date":"2023","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/37414147","citation_count":11,"is_preprint":false},{"pmid":"28936467","id":"PMC_28936467","title":"Peroxisome Motility Measurement and Quantification Assay.","date":"2017","source":"Bio-protocol","url":"https://pubmed.ncbi.nlm.nih.gov/28936467","citation_count":9,"is_preprint":false},{"pmid":"39271061","id":"PMC_39271061","title":"New insights into the functions of ACBD4/5-like proteins using a combined phylogenetic and experimental approach across model organisms.","date":"2024","source":"Biochimica et biophysica acta. Molecular cell research","url":"https://pubmed.ncbi.nlm.nih.gov/39271061","citation_count":7,"is_preprint":false},{"pmid":"39394562","id":"PMC_39394562","title":"Genetic architectures of the human hippocampus and those involved in neuropsychiatric traits.","date":"2024","source":"BMC medicine","url":"https://pubmed.ncbi.nlm.nih.gov/39394562","citation_count":4,"is_preprint":false},{"pmid":"36952197","id":"PMC_36952197","title":"Assessing Peroxisomal Protein Interaction by Immunoprecipitation.","date":"2023","source":"Methods in molecular biology (Clifton, N.J.)","url":"https://pubmed.ncbi.nlm.nih.gov/36952197","citation_count":1,"is_preprint":false},{"pmid":"40873809","id":"PMC_40873809","title":"Acyl-coA binding protein AcbdA regulates peroxisome hitchhiking on early endosomes.","date":"2025","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/40873809","citation_count":1,"is_preprint":false},{"pmid":"40901736","id":"PMC_40901736","title":"Acyl-CoA-binding protein AcbdA is required for peroxisome hitchhiking on early endosomes in Aspergillus nidulans.","date":"2025","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/40901736","citation_count":0,"is_preprint":false},{"pmid":"40570459","id":"PMC_40570459","title":"Multi-omics analysis provides new insights into molecular mechanisms for waterfowl fatty liver formation.","date":"2025","source":"Poultry science","url":"https://pubmed.ncbi.nlm.nih.gov/40570459","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":9156,"output_tokens":1418,"usd":0.024369,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8103,"output_tokens":1977,"usd":0.04497,"stage2_stop_reason":"end_turn"},"total_usd":0.069339,"stage1_batch_id":"msgbatch_0179Z2pxRYBsXi2xADneafRw","stage2_batch_id":"msgbatch_01LaY9ZaVdgjWArcZo9eqQE5","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2017,\n      \"finding\": \"ACBD4 is a tail-anchored peroxisomal membrane protein that interacts with the ER protein VAPB (vesicle-associated membrane protein-associated protein B) to promote peroxisome-ER membrane contact site associations.\",\n      \"method\": \"Molecular cell biology characterization of ACBD4 as tail-anchored peroxisomal membrane protein; interaction with VAPB demonstrated; overexpression/loss-of-function showing altered peroxisome-ER associations\",\n      \"journal\": \"Cell cycle (Georgetown, Tex.)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal protein interaction data combined with localization experiments and functional consequence (altered peroxisome-ER contacts), replicated in subsequent independent studies\",\n      \"pmids\": [\"28463579\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Loss of ACBD4 does not reduce peroxisome-ER connections or result in accumulation of very long-chain fatty acids (VLCFAs); instead, loss of ACBD4 increases the rate of peroxisomal β-oxidation of VLCFAs, suggesting a regulatory rather than primary tethering role at the peroxisome-ER interface. Additionally, ACBD4 interacts with ACBD5 independently of VAPB binding.\",\n      \"method\": \"Loss-of-function (ACBD4 knockout in HEK293 cells) combined with molecular cell biology, biochemical assays, and lipidomics; co-immunoprecipitation for ACBD4-ACBD5 interaction\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (KO, lipidomics, Co-IP) in a single rigorous study establishing mechanistic distinction from ACBD5\",\n      \"pmids\": [\"37414147\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"ACBD4 and ACBD5 function as peroxisomal tethering components that physically interact with ER-resident VAPB to form peroxisome-ER membrane contact sites; overexpression or loss of these tether proteins alters the extent of peroxisome-ER interactions and impacts lipid exchange between the two compartments.\",\n      \"method\": \"Proximity ligation assay and split superfolder GFP reporter system to monitor peroxisome-ER interactions; manipulation of tether protein levels with quantification of contact site changes\",\n      \"journal\": \"Contact (Thousand Oaks (Ventura County, Calif.))\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — two orthogonal fluorescence-based assays used to validate contact site tethering function, single lab but multiple methods\",\n      \"pmids\": [\"31198905\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"The FFAT motif in ACBD4 mediates interaction with ER-resident VAP proteins to tether peroxisomes to the ER; this FFAT-VAP tethering function is conserved in Drosophila ACBD4/5-like protein (which has a functional FFAT motif tethering peroxisomes to the ER via Dm_Vap33), while the fungal Ustilago maydis ACBD4/5-like protein lacks a functional FFAT motif and does not interact with Um_Vap33.\",\n      \"method\": \"Phylogenetic analysis combined with experimental validation: FFAT motif functional assays, co-localization and interaction studies in Drosophila and fungal model organisms, depletion experiments showing peroxisome redistribution\",\n      \"journal\": \"Biochimica et biophysica acta. Molecular cell research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — combined phylogenetic and experimental approach across model organisms, multiple cell biology methods, but primarily in non-human model systems for the mechanistic validation\",\n      \"pmids\": [\"39271061\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"ACBD4 (and its paralog ACBD5) bind ER membrane protein VAPB to mediate peroxisome-ER contacts; immunoprecipitation can be used to identify residues important for regulation of this interaction, including phosphorylation sites.\",\n      \"method\": \"Immunoprecipitation with antibody-conjugated beads followed by western blot analysis; domain deletion and mutagenesis to identify interaction determinants including phosphorylation\",\n      \"journal\": \"Methods in molecular biology (Clifton, N.J.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — immunoprecipitation-based interaction study with domain analysis, single lab, methods paper context\",\n      \"pmids\": [\"36952197\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"ACBD4 is a tail-anchored peroxisomal membrane protein that uses its FFAT motif to interact with ER-resident VAPB, forming peroxisome-ER membrane contact sites; while its paralog ACBD5 acts as the primary tether and VLCFA recruitment factor, ACBD4 plays a regulatory role in peroxisomal β-oxidation of very long-chain fatty acids and also interacts with ACBD5 independently of VAPB.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"ACBD4 is a tail-anchored peroxisomal membrane protein that helps organize peroxisome-endoplasmic reticulum membrane contact sites and modulates peroxisomal lipid metabolism [#0, #1]. It uses an FFAT motif to bind the ER-resident protein VAPB, and overexpression or loss of ACBD4 alters the extent of peroxisome-ER associations [#0, #3]. This FFAT-VAP tethering function is evolutionarily conserved, being retained in the Drosophila ACBD4/5-like protein but lost in the fungal Ustilago maydis ortholog, which lacks a functional FFAT motif [#3]. Functionally, ACBD4 plays a regulatory rather than primary tethering role: its loss does not reduce peroxisome-ER connections or cause very long-chain fatty acid accumulation but instead increases the rate of peroxisomal β-oxidation of VLCFAs, distinguishing it mechanistically from its paralog ACBD5 [#1]. ACBD4 also interacts directly with ACBD5 independently of VAPB binding [#1]. Beyond these contact-site and metabolic regulatory roles, no further mechanistic detail has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2017,\n      \"claim\": \"Established ACBD4 as a peroxisomal membrane protein and assigned it a role in inter-organelle contact, answering whether it physically links peroxisomes to another compartment.\",\n      \"evidence\": \"Characterization as a tail-anchored peroxisomal protein with demonstrated VAPB interaction and altered peroxisome-ER associations on manipulation\",\n      \"pmids\": [\"28463579\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not distinguish whether ACBD4 is a primary tether or a regulatory factor\", \"No functional consequence for lipid metabolism established\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Quantified the contact-site tethering activity of ACBD4 and linked peroxisome-ER contacts to lipid exchange, addressing the functional output of these junctions.\",\n      \"evidence\": \"Proximity ligation and split-superfolder-GFP reporter assays with tether-level manipulation\",\n      \"pmids\": [\"31198905\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single-lab fluorescence assays\", \"Did not separate ACBD4-specific from ACBD5-specific contributions\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Distinguished ACBD4 from ACBD5 by showing ACBD4 loss does not impair tethering or cause VLCFA accumulation but accelerates β-oxidation, establishing a regulatory rather than tethering role and a VAPB-independent ACBD5 interaction.\",\n      \"evidence\": \"ACBD4 knockout in HEK293 cells with lipidomics, biochemical assays, and co-immunoprecipitation\",\n      \"pmids\": [\"37414147\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular basis for accelerated β-oxidation upon ACBD4 loss unresolved\", \"Functional consequence of ACBD4-ACBD5 interaction unknown\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Identified interaction determinants, including phosphorylation sites, as candidate regulators of ACBD4-VAPB binding.\",\n      \"evidence\": \"Immunoprecipitation with domain deletion and mutagenesis (methods paper context)\",\n      \"pmids\": [\"36952197\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional impact of specific phosphorylation sites not demonstrated\", \"Kinase and regulatory context unknown\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Mapped the FFAT motif as the VAP-binding element and traced its evolutionary conservation, clarifying the structural basis and phylogenetic distribution of ACBD4-mediated tethering.\",\n      \"evidence\": \"Phylogenetic analysis with FFAT functional assays and interaction/depletion studies in Drosophila and Ustilago maydis\",\n      \"pmids\": [\"39271061\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanistic validation primarily in non-human model organisms\", \"Structural model of the FFAT-VAP interface not resolved\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How ACBD4 mechanistically restrains the rate of peroxisomal VLCFA β-oxidation, and how its VAPB-independent association with ACBD5 fits into contact-site assembly, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No molecular mechanism linking ACBD4 to β-oxidation rate control\", \"Role of the ACBD4-ACBD5 complex undefined\", \"No structural data on the contact-site assembly\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 2, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005777\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0005783\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1430728\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [\"peroxisome-ER membrane contact site\"],\n    \"partners\": [\"VAPB\", \"ACBD5\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}