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Primary mouse microglia and HMC3 cells were used to examine ABI3 function and\n                      <jats:italic>S209F<\/jats:italic>\n                      effects. Liquid\u2013liquid phase separation (LLPS) properties were characterized in cellular systems and with recombinant proteins.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      ABI3 was highly expressed in AD microglia. ABI3 enhanced microglial clustering around amyloid beta (A\u03b2) plaques, promoted A\u03b2 clearance, and ameliorated cognitive decline, whereas\n                      <jats:italic>S209F<\/jats:italic>\n                      abolished these effects. Mechanistically, ABI3 undergoes LLPS essential for microglial migration and phagocytosis. The S209 residue lies within an intrinsic disordered region, and\n                      <jats:italic>S209F<\/jats:italic>\n                      disrupts phosphorylation\u2010dependent LLPS, thereby impairing microglial functions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>\n                      The AD\u2010associated\n                      <jats:italic>ABI3 S209F<\/jats:italic>\n                      variant drives pathogenesis by disrupting LLPS, causing microglial dysfunction. Enhancing ABI3 phase separation represents a potential therapeutic strategy to boost microglial activity against A\u03b2 pathology.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71812","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T09:28:52Z","timestamp":1790242132000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Aberrant phase separation from a rare\n                    <i>ABI3<\/i>\n                    mutation drives microglial dysfunction and Alzheimer's risk"],"prefix":"10.1002","volume":"22","author":[{"given":"Shengnan","family":"Li","sequence":"first","affiliation":[{"name":"Institute of Neurology, Guangdong Key Laboratory of Age\u2010Related Cardiac and Cerebral Diseases Affiliated Hospital of Guangdong Medical University  Zhanjiang 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