biostudies-literatureUnknown45(4)Zhu YFAutophagy plays a pivotal role in diverse biological processes, including the maintenance and differentiation of neural stem cells (NSCs). Interestingly, while complete deletion of <i>Fip200</i> severely impairs NSC maintenance and differentiation, inhibiting canonical autophagy via deletion of core genes, such as <i>Atg5</i>, <i>Atg16l1</i>, and <i>Atg7</i>, or blockade of canonical interactions between FIP200 and ATG13 (designated as FIP200-4A mutant or FIP200 KI) does not produce comparable detrimental effects. This highlights the likely critical involvement of the non-canonical functions of FIP200, the mechanisms of which have remained elusive. Here, utilizing genetic mouse models, we demonstrated that FIP200 mediates non-canonical autophagic degradation of p62/sequestome1, primarily vZoological research937-950https://www.ebi.ac.uk/biostudies/studies/S-EPMC11298671biostudies-literatureTAX1BP1 and FIP200 orchestrate non-canonical autophagy of p62 aggregates for mouse neural stem cell maintenance.PMC11298671Yu RHThorne RFWu MZhang JLZhu YFZhou SXu RZhang YWZhang RShi XJTang PPZhang XDLiu GZWang YYChen SWei JMWu YXLi MKfalseTAX1BP1 and FIP200 orchestrate non-canonical autophagy of p62 aggregates for mouse neural stem cell maintenance.Autophagy plays a pivotal role in diverse biological processes, including the maintenance and differentiation of neural stem cells (NSCs). Interestingly, while complete deletion of <i>Fip200</i> severely impairs NSC maintenance and differentiation, inhibiting canonical autophagy via deletion of core genes, such as <i>Atg5</i>, <i>Atg16l1</i>, and <i>Atg7</i>, or blockade of canonical interactions between FIP200 and ATG13 (designated as FIP200-4A mutant or FIP200 KI) does not produce comparable detrimental effects. This highlights the likely critical involvement of the non-canonical functions of FIP200, the mechanisms of which have remained elusive. Here, utilizing genetic mouse models, we demonstrated that FIP200 mediates non-canonical autophagic degradation of p62/sequestome1, primarily v2024-01-01T00:00:00Z2024 Jul2025-04-05T15:03:20.575Z2025-02-19T04:40:34.299ZS-EPMC112986713902108210.24272/j.issn.2095-8137.2024.021