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Compromised gut barrier due to IEC apoptosis promotes bacterial translocation and inflammatory responses, which in turn escalates to further IEC death and barrier defects. Nevertheless, the precise mechanisms that safeguard IECs from apoptosis and interrupt this vicious cycle are yet to be elucidated. Here, we report that Grb2\u2010associated binder 1 (Gab1) expression is diminished in the intestines of both septic patients and established sepsis models. Epithelial Gab1 deficiency rendered mice susceptible to lipopolysaccharide (LPS)\u2010induced sepsis by sensitizing IECs to apoptosis, thereby contributing to systemic inflammation and markedly exacerbating septic lethality. Mechanistically, Gab1 mitigated apoptotic signaling via IKK\u03b2\u2010dependent NF\u2010\u03baB activation and subsequent transcriptional regulation of apoptotic genes in response to TNF\u2010\u03b1. Collectively, our findings define a protective role for Gab1 in sepsis\u2010induced intestinal injury by sustaining apoptotic balance and intestinal homeostasis, which provides new insights into therapeutic strategies for sepsis management, particularly those aiming at restoring immune homeostasis and improving barrier function.<\/jats:p>","DOI":"10.1155\/mi\/5486971","type":"journal-article","created":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T13:13:21Z","timestamp":1769865201000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Epithelial Gab1 Restricts Sepsis\u2010Induced Intestinal Injury by Orchestrating TNF\/NF\u2010\u03baB 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