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Here, we investigated whether loss of MUNC18\u20101 causes defects in intracellular membrane transport pathways in primary murine neurons that may explain neurodegeneration. Electron, confocal and super resolution microscopy confirmed that loss of MUNC18\u20101 expression results in a smaller <jats:italic>cis\u2010<\/jats:italic>Golgi. In addition, we now show that <jats:italic>medial<\/jats:italic>\u2010Golgi and the <jats:italic>trans\u2010<\/jats:italic>Golgi Network are also affected. However, stacking and cisternae ultrastructure of the Golgi were normal. Overall, ultrastructure of null mutant neurons was remarkably normal just hours before cell death occurred. By synchronizing protein trafficking by conditional cargo retention in the endoplasmic reticulum using selective hooks (RUSH) and immunocytochemistry, we show that anterograde Endoplasmic Reticulum\u2010to\u2010Golgi and Golgi exit of endogenous and exogenous proteins were normal. In contrast, loss of MUNC18\u20101 caused reduced retrograde Cholera Toxin B\u2010subunit transport from the plasma membrane to the Golgi. In addition, MUNC18\u20101\u2010deficiency resulted in abnormalities in retrograde TrkB trafficking in an antibody uptake assay. We conclude that MUNC18\u20101 deficient neurons have normal anterograde but reduced retrograde transport to the Golgi. The impairments in retrograde pathways suggest a role of MUNC18\u20101 in endosomal SNARE\u2010dependent fusion and provide a plausible explanation for the observed Golgi abnormalities and cell death in MUNC18\u20101 deficient neurons.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc15256-fig-0008-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.15256","type":"journal-article","created":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T23:45:08Z","timestamp":1606866308000},"page":"450-466","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Loss of MUNC18\u20101 leads to retrograde transport defects in neurons"],"prefix":"10.1111","volume":"157","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1046-8091","authenticated-orcid":false,"given":"Annemiek A.","family":"van Berkel","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics Center for Neurogenomics and Cognitive Research (CNCR) University Medical Center Amsterdam Amsterdam The Netherlands"},{"name":"Department of Functional Genomics Center for Neurogenomics and Cognitive Research (CNCR) VU University Amsterdam Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatiana C.","family":"Santos","sequence":"additional","affiliation":[{"name":"Department of Functional Genomics Center for Neurogenomics and Cognitive Research (CNCR) VU University Amsterdam Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0507-2858","authenticated-orcid":false,"given":"Hesho","family":"Shaweis","sequence":"additional","affiliation":[{"name":"Department of Functional Genomics Center for Neurogenomics and Cognitive Research (CNCR) VU University Amsterdam Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5259-4945","authenticated-orcid":false,"given":"Jan R. 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