{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:58:49Z","timestamp":1790395129800,"version":"4.1.0"},"reference-count":57,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DP2NS136873"],"award-info":[{"award-number":["DP2NS136873"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32NS007431"],"award-info":[{"award-number":["T32NS007431"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P50HD103573"],"award-info":[{"award-number":["P50HD103573"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30CA016086"],"award-info":[{"award-number":["P30CA016086"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1S10OD030300"],"award-info":[{"award-number":["1S10OD030300"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["2P30CA016086\u201045"],"award-info":[{"award-number":["2P30CA016086\u201045"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U24NS124025"],"award-info":[{"award-number":["U24NS124025"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Glia"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare leukodystrophy characterized by early\u2010onset macrocephaly, white matter edema, seizures, and motor and cognitive decline. Approximately 25% of MLC patients carry\n                    <jats:italic>HEPACAM<\/jats:italic>\n                    pathogenic variants, many of which are dominant missense variants causing remitting MLC Type 2b.\n                    <jats:italic>HEPACAM<\/jats:italic>\n                    encodes hepatic and glial cell adhesion molecule (hepaCAM), also known as GlialCAM, an astrocyte\u2010enriched transmembrane protein with important roles in astrocyte territory establishment, gap junction coupling, branching organization, synaptic function, and development of the gliovascular unit. The molecular mechanisms through which pathogenic variants in\n                    <jats:italic>HEPACAM<\/jats:italic>\n                    alter hepaCAM protein function in\u00a0vivo and facilitate MLC pathogenesis during brain development remain largely unknown. Here, we used new viral tools and proximity\u2010based proteomics to examine how three different dominant pathogenic variants alter hepaCAM subcellular localization and protein interactome in astrocytes of the developing mouse cortex. We found dramatic changes in hepaCAM distribution throughout the astrocyte, which were common to all mutants tested. We also observed significant changes in protein interactome between wild type and mutant hepaCAM, including decreased association with previously described hepaCAM\u2010interacting proteins Connexin 43 and CLC\u20102. Moreover, we identified the epilepsy\u2010associate potassium channel KCNQ2 as a novel hepaCAM interaction partner and found reduced association between KCNQ2 and pathogenic variants. Collectively, our data provide new insights into hepaCAM protein function in astrocytes during brain development, reveal altered protein dynamics of pathogenic variants, and provide a new resource to explore the molecular underpinnings of MLC pathogenesis.\n                  <\/jats:p>","DOI":"10.1002\/glia.70218","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T03:07:12Z","timestamp":1787800032000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pathogenic Variants in\n                    <scp>\n                      <i>HEPACAM<\/i>\n                    <\/scp>\n                    Alter Protein Localization and Interactome in Astrocytes of the Developing Mouse Cortex"],"prefix":"10.1002","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0085-8385","authenticated-orcid":false,"given":"Robert W.","family":"Lewis","sequence":"first","affiliation":[{"name":"Neuroscience Center University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Breana C.","family":"Dogan","sequence":"additional","affiliation":[{"name":"Neuroscience Center University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy L.","family":"Stanek","sequence":"additional","affiliation":[{"name":"Neuroscience Center University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6339-969X","authenticated-orcid":false,"given":"Elliot B.","family":"Evans","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5394-924X","authenticated-orcid":false,"given":"Madelyn G.","family":"Coble","sequence":"additional","affiliation":[{"name":"Neuroscience Center University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9565-5856","authenticated-orcid":false,"given":"Hayli E.","family":"Spence\u2010Osorio","sequence":"additional","affiliation":[{"name":"Neuroscience Center University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen L. G.","family":"Farizatto","sequence":"additional","affiliation":[{"name":"Neuroscience Center University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angie L.","family":"Mordant","sequence":"additional","affiliation":[{"name":"Metabolomics and Proteomics Core Facility, Department of Pharmacology University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Allie","family":"Mills","sequence":"additional","affiliation":[{"name":"Metabolomics and Proteomics Core Facility, Department of Pharmacology University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4496-7312","authenticated-orcid":false,"given":"Laura E.","family":"Herring","sequence":"additional","affiliation":[{"name":"Metabolomics and Proteomics Core Facility, Department of Pharmacology University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4423-5712","authenticated-orcid":false,"given":"Katherine T.","family":"Baldwin","sequence":"additional","affiliation":[{"name":"Neuroscience Center University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"},{"name":"Department of Cell Biology and Physiology University of North Carolina at Chapel 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