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In these compartments, cGAS assumes distinct regulatory states and executes specialised functions. For instance, chromatin\u2010bound nuclear cGAS remains inactive under homeostasis but contributes to genome maintenance during genotoxic stress, whereas mitochondrial or micronuclear cGAS links damage signals to inflammation and cell death. This review synthesises recent advances in the spatial regulation of cGAS, focusing on mechanisms such as membrane interactions and post\u2010translational modifications. We further reframe cGAS as a multifunctional regulator in infection, cancer, autoimmunity, and ageing, and introduce a unifying \u2018location code\u2019 framework. This framework proposes that the combined influence of PTMs, protein interactions, and membrane affinities dictates cGAS localisation, functional output, and pathological outcomes, thereby paving the way for spatially informed therapeutic interventions.\n                  <\/jats:p>","DOI":"10.1111\/imm.70133","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T15:32:01Z","timestamp":1773847921000},"page":"582-614","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Inside Out: How Cellular Localisation Shapes\n                    <scp>cGAS<\/scp>\n                    Functions in Health and Disease"],"prefix":"10.1111","volume":"178","author":[{"given":"Jiaqi","family":"Wu","sequence":"first","affiliation":[{"name":"The Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, School of Medicine University of Electronic Science and Technology of China  Chengdu China"},{"name":"Research Unit for Blindness Prevention of the Chinese Academy of Medical Sciences Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital  Chengdu China"},{"name":"School of Medicine, University of Electronic Science and Technology of China  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Zhou","sequence":"additional","affiliation":[{"name":"The Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, School of Medicine University of Electronic Science and Technology of China  Chengdu China"},{"name":"Research Unit for Blindness Prevention of the Chinese Academy of Medical Sciences Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital  Chengdu China"},{"name":"School of Medicine, University of Electronic Science and Technology of China  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Zeng","sequence":"additional","affiliation":[{"name":"The Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, School of Medicine University of Electronic Science and Technology of China  Chengdu China"},{"name":"Research Unit for Blindness Prevention of the Chinese Academy of Medical Sciences Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital  Chengdu China"},{"name":"School of Medicine, University of Electronic Science and Technology of China  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Electronic Science and Technology of China  Chengdu 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