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Fatty acid binding protein 5 (FABP5), a lipid chaperone, has been implicated in chronic inflammation. However, whether FABP5 regulates pyroptosis and its pathological role in epilepsy remains uncharacterized. Here, FABP5 was upregulated in astrocytes from temporal lobe epilepsy (TLE) patients, epileptic mice, and primary cells. Deletion of astrocytic\n                    <jats:italic>Fabp5<\/jats:italic>\n                    significantly attenuated pyroptosis, neuronal loss, and seizure activity in epilepsy. Furthermore, cyclic GMP\u2010AMP synthase (cGAS)\u2010stimulator of interferon genes (STING) pathway was identified as the downstream signaling of FABP5 by RNA sequencing analysis. Mechanistically,\n                    <jats:italic>Fabp5<\/jats:italic>\n                    knockdown reduced lipid overload, alleviated mitochondrial dysfunction, and suppressed cGAS\u2010STING activation. Pharmacological inhibition of mitochondrial fatty acid import recapitulated these protective effects. In contrast,\n                    <jats:italic>Sting<\/jats:italic>\n                    overexpression abolished the reduced pyroptosis level by\n                    <jats:italic>Fabp5<\/jats:italic>\n                    knockdown, whereas STING inhibition using C\u2010176 attenuated pyroptosis and seizure activity. Collectively, these findings revealed the regulatory role of FABP5\u2010cGAS\u2010STING\u2010pyroptosis axis in the progression of epilepsy and highlighted the promising potential of astrocytic FABP5 as a therapeutic target for epilepsy.\n                  <\/jats:p>","DOI":"10.1002\/advs.76377","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T15:56:22Z","timestamp":1783353382000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Fatty Acid Binding Protein 5 Mediates Astrocytic Pyroptosis and Neuroinflammation in Epilepsy via cGAS\/STING Pathway"],"prefix":"10.1002","volume":"13","author":[{"given":"Chen","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Neurology Zhongshan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department 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