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These filaments scaffold the innermost non\u2010compacted myelin layer; their disruption causes pathological myelin outfoldings. However, the mechanisms that control myelin septin assembly are incompletely understood. We found that loss of CDC42 from oligodendrocytes of adult mice causes myelin pathology including outfoldings, coinciding with depletion of myelin septins and CDC42\u2010effector proteins (CDC42EP1 and CDC42EP2). We thus tested the functional relevance of the latter by deleting both the\n                    <jats:italic>Cdc42ep1<\/jats:italic>\n                    and\n                    <jats:italic>Cdc42ep2<\/jats:italic>\n                    \u2010genes in oligodendrocytes. We observed myelin outfoldings as a very specific pathology, markedly reduced abundance of myelin septins, and disorganized septin filaments in myelin. Immunohistochemical analysis did not uncover astrocyte or microglial activation, implying that myelin outfoldings per se do not induce secondary neuropathology. Together, our data reveal a critical function for CDC42 and CDC42EP1\/CDC42EP2 in regulating myelin septin filaments, which facilitate structural integrity of myelin sheaths.\n                  <\/jats:p>","DOI":"10.1002\/glia.70134","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T16:11:49Z","timestamp":1767715909000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>CDC42<\/scp>\n                    \u2010Effector Proteins Regulate Higher Order Structure of Septins Required for\n                    <scp>CNS<\/scp>\n                    Myelin Integrity"],"prefix":"10.1002","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-3787-2043","authenticated-orcid":false,"given":"Sophie","family":"H\u00fcmmert","sequence":"first","affiliation":[{"name":"Department of Neurogenetics Max Planck Institute for Multidisciplinary Sciences  G\u00f6ttingen 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