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This review explores the pivotal role of mitogen\u2010activated protein kinase (MAPK) signaling in modulating inflammasome activation through various regulatory mechanisms. We detail recent advances in understanding MAPK\u2010mediated regulation of NLRP3 inflammasome priming, licensing and activation, with emphasis on MAPK\u2010induced activator protein\u20101 (AP\u20101) signaling in NLRP3 priming, ERK1 and JNK in NLRP3 licensing, and TAK1 in connecting death receptor signaling to NLRP3 inflammasome activation. Furthermore, we discuss novel insights into MAPK signaling in human NLRP1 inflammasome activation, focusing on the MAP3K member ZAK\u03b1 as a key kinase linking ribosomal stress to inflammasome activation. Lastly, we review recent work elucidating how <jats:styled-content style=\"fixed-case\"><jats:italic>Bacillus anthracis<\/jats:italic><\/jats:styled-content> lethal toxin (LeTx) manipulates host MAPK signaling to induce macrophage apoptosis as an immune evasion strategy, and the counteraction of this effect through genotype\u2010specific Nlrp1b inflammasome activation in certain rodent strains.<\/jats:p>","DOI":"10.1111\/imr.13436","type":"journal-article","created":{"date-parts":[[2025,1,4]],"date-time":"2025-01-04T08:04:37Z","timestamp":1735977877000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["MAP Kinase Signaling at the Crossroads of Inflammasome Activation"],"prefix":"10.1111","volume":"329","author":[{"given":"Alex","family":"Vervaeke","sequence":"first","affiliation":[{"name":"Department of Internal Medicine and Paediatrics Ghent University  Ghent 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