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Despite typically late onset and slow progression, the molecular basis of age\u2010related decline remains unclear. We used a somatic in\u00a0vivo approach to express wild\u2010type (WT) PKC\u03b3\u2013GFP or the prototypical G128D PKC\u03b3\u2013GFP selectively in PCs of neonatal mice via an adeno\u2010associated virus (AAV) under a PC\u2010specific promoter. G128D PKC\u03b3\u2013GFP formed cytoplasmic aggregates, mislocalized PCs during development, and produced gait deficits by 4\u2009weeks that worsened with age, despite preserved PC counts and overall cerebellar volume at 1.5\u2009years. Immunohistochemistry revealed a selective vulnerability of climbing\u2010fiber (CF) input: vesicular glutamate transporter 2 (VGLUT2), a marker of CF synapses, declined significantly from 12 to 60\u2009weeks in G128D mice, and the VGLUT2\u2010positive innervation field was narrower than age\u2010matched WT at both time points. By contrast, the glutamate\/aspartate transporter GLAST in Bergmann\u2010glial radial processes was reduced predominantly at 12\u2009weeks in G128D mice. The \u03b42 glutamate receptor (GluD2) at parallel fibers and glial fibrillary acidic protein (GFAP) decreased with age but were comparable between expression conditions. Notably, aggregated mutant PKC\u03b3 accumulated within the axon initial segment (AIS), whose architecture progressively deteriorated; the altered AIS excluded PKC\u03b3\u2013GFP from distal axons and, by 60\u2009weeks, was associated with reduced delivery of the vesicular GABA transporter (VGAT) to deep cerebellar nuclei (DCN), consistent with impaired anterograde transport. Hence, rather than overt neuronal loss, the cumulative burden of G128D\u2010specific CF\/axonal deficits and age\u2010accentuated circuit and glial changes\u2014reduced GLAST function and decreased GluD2\u2014accounts\u00a0for the worsening motor phenotype. This AAV\u2010based system provides a practical platform to dissect late\u2010onset pathogenic mechanisms and evaluate therapeutic strategies in\u00a0vivo.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70305-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70305","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T09:31:02Z","timestamp":1764063062000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Age\u2010Progressive Synaptic and Axonal Dysregulation Induced by Purkinje Cell\u2013Targeted\n                    <scp>AAV<\/scp>\n                    Expression of\n                    <scp>SCA14 PKC\u03b3<\/scp>\n                    in Mice"],"prefix":"10.1111","volume":"169","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8797-0717","authenticated-orcid":false,"given":"Naoko","family":"Adachi","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Pharmacology, Biosignal Research Center Kobe University  Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Izumi","family":"Koganemaru","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pharmacology, Biosignal Research Center Kobe University  Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Wanying","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pharmacology, Biosignal Research Center Kobe University  Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoya","family":"Matsushita","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pharmacology, Biosignal Research Center Kobe University  Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoyoshi","family":"Nakayama","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pharmacology, Biosignal Research Center Kobe University  Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takahiro","family":"Seki","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmaceutical Sciences Himeji\u2010Dokkyo University  Himeji Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9382-396X","authenticated-orcid":false,"given":"Ayumu","family":"Konno","sequence":"additional","affiliation":[{"name":"Department of Neurophysiology &amp; Neural Repair Gunma University Graduate School of Medicine  Maebashi Gunma Japan"},{"name":"Viral Vector Core Gunma University, Initiative for Advanced Research  Maebashi Gunma Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirokazu","family":"Hirai","sequence":"additional","affiliation":[{"name":"Department of Neurophysiology &amp; Neural Repair Gunma University Graduate School of Medicine  Maebashi Gunma Japan"},{"name":"Viral Vector Core Gunma University, Initiative for Advanced Research  Maebashi Gunma Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoaki","family":"Saito","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pharmacology, Biosignal Research Center Kobe University  Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5647-3937","authenticated-orcid":false,"given":"Takehiko","family":"Ueyama","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pharmacology, Biosignal Research Center Kobe University  Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,11,25]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M801492200"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbrainres.2005.06.007"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90205-4"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.2579\u201011.2011"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1094\u2010136"},{"key":"e_1_2_11_7_1","unstructured":"Byrne J. 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