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NLRP1 and CARD8 are related germline\u2010encoded pattern recognition receptors that form inflammasomes, but their activation mechanisms and biological purposes have not yet been fully established. Both NLRP1 and CARD8 undergo post\u2010translational autoproteolysis to generate two non\u2010covalently associated polypeptide chains. NLRP1 and CARD8 activators induce the proteasome\u2010mediated destruction of the N\u2010terminal fragment, liberating the C\u2010terminal fragment to form an inflammasome. Here, we review the danger\u2010associated stimuli that have been reported to activate NLRP1 and\/or CARD8, including anthrax lethal toxin, <jats:italic>Toxoplasma gondii, Shigella flexneri<\/jats:italic> and the small molecule DPP8\/9 inhibitor Val\u2010boroPro, focusing on recent mechanistic insights and highlighting unresolved questions. In addition, we discuss the recently identified disease\u2010associated mutations in NLRP1 and CARD8, the potential role that DPP9\u2019s protein structure plays in inflammasome regulation, and the emerging link between NLRP1 and metabolism. Finally, we summarize all of this latest research and consider the possible biological purposes of these enigmatic inflammasomes.<\/jats:p>","DOI":"10.1111\/imr.12884","type":"journal-article","created":{"date-parts":[[2020,6,19]],"date-time":"2020-06-19T14:00:03Z","timestamp":1592575203000},"page":"13-25","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":182,"title":["The NLRP1 and CARD8 inflammasomes"],"prefix":"10.1111","volume":"297","author":[{"given":"Cornelius Y.","family":"Taabazuing","sequence":"first","affiliation":[{"name":"Chemical Biology Program Memorial Sloan Kettering Cancer Center New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew R.","family":"Griswold","sequence":"additional","affiliation":[{"name":"Weill Cornell, Rockefeller, Sloan Kettering Tri\u2010Institutional MD\u2010PhD Program New York NY USA"},{"name":"Pharmacology Program of the Weill Cornell Graduate School of 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