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However, the molecular composition of cell type\u2010specific brain EVs, particularly astrocyte\u2010derived EVs (ADEVs), remains poorly defined. We performed comparative proteomic analysis of neuronal (NDEVs), microglial (MDEVs), and ADEVs from mouse brain using magnetic immunocapture and LC\u2013MS\/MS proteomic profiling. Each EV subtype displayed distinct molecular fingerprints. NDEVs were enriched in synaptic and neurogenesis\u2010related proteins (e.g., APP, SNAP25, GPR158, and BDNF), whereas MDEVs contained immune and phagocytic markers (e.g., TMEM119, CX3CR1, CD11b). Strikingly, the ADEV proteome closely mirrored the recently characterized GlialCAM interactome from leukodystrophy research, encompassing GlialCAM\/MLC1 and associated partners involved in ion and water homeostasis (EAAT1\/2, AQP4, GJA1), together with GPCRs such as GPRC5B. This overlap suggests that ADEVs encapsulate a molecular scaffold characteristic of astrocytic endfeet, potentially extending their signaling functions to the extracellular space. In conclusion, our study provides a detailed comparative proteomic characterization of brain cell type\u2010specific EVs, revealing that ADEVs contain the GlialCAM\/MLC1 network and GPCRs. These findings identify candidate molecular signatures that support the future investigation of ADEVs for biomarker development and provide a proteomic framework for exploring their relationship with astrocytic endfoot biology, blood\u2013brain barrier (BBB)\u2010associated pathways, and neurodegenerative disorders.<\/jats:p>","DOI":"10.1002\/glia.70212","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T14:22:40Z","timestamp":1787322160000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cell Type\u2010Specific Extracellular Vesicles in Mouse Brain: Proteomic Signatures Highlight Astrocytic\n                    <scp>GlialCAM<\/scp>\n                    Network and\n                    <scp>GPCR<\/scp>\n                    Enrichment"],"prefix":"10.1002","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1158-8765","authenticated-orcid":false,"given":"Alba 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