Aggregation　of　aberrant　proteins　is　a　common　pathological　hallmark　in　neurodegeneration　such　as　polyglutamine　(polyQ)　and　other　repeat-expansion　diseases.　Here　through　overexpression　of　ataxin3　C-terminal　polyQ　expansion　in　Drosophila　gut　enterocytes,　we　generated　an　intestinal　obstruction　model　of　spinocerebellar　ataxia　type3　(SCA3)　and　reported　a　new　role　of　nuclear-associated　endosomes　(NAEs)-the　delivery　of　polyQ　to　the　nucleoplasm.　In　this　model,　accompanied　by　the　prominently　increased　RAB5-positive　NAEs　are　abundant　nucleoplasmic　reticulum　enriched　with　polyQ,　abnormal　nuclear　envelope　invagination,　significantly　reduced　endoplasmic　reticulum,　indicating　dysfunctional　nucleocytoplasmic　trafficking　and　impaired　endomembrane　organization.　Consistently,　Rab5　but　not　Rab7　RNAi　further　decreased　polyQ-related　NAEs,　inhibited　endomembrane　disorganization,　and　alleviated　disease　model.　Interestingly,　autophagic　proteins　were　enriched　in　polyQ-related　NAEs　and　played　non-canonical　autophagic　roles　as　genetic　manipulation　of　autophagic　molecules　exhibited　differential　impacts　on　NAEs　and　SCA3　toxicity.　Namely,　the　down-regulation　of　Atg1　or　Atg12　mitigated　while　Atg5　RNAi　aggravated　the　disease　phenotypes　both　in　Drosophila　intestines　and　compound　eyes.　Our　findings,　therefore,　provide　new　mechanistic　insights　and　underscore　the　fundamental　roles　of　endosome-centered　nucleocytoplasmic　trafficking　and　homeostatic　endomembrane　allocation　in　the　pathogenesis　of　polyQ　diseases.