NLRP1 under pressure: An overview of the NLRP1 inflammasome as a sensor of cellular stress.

NLRP1 (NACHT, leucine-rich repeats [LRRs], and pyrin domain [PYD]-containing protein 1) is a microbe and stress sensor that, upon activation, forms a caspase-1-activating inflammasome that drives IL-1β and IL-18 maturation and pyroptotic cell death. NLRP1 exhibits allelic diversity and interspecies differences in protein architecture, activating stimuli and expression patterns. Despite this complexity, human NLRP1 is emerging as an important sensor of perturbations in epithelial homeostasis, with key functions in epithelial inflammation, integrity, and barrier function. Here, we review recent discoveries of NLRP1 activation pathways, insights that may be gained from the related proteins caspase recruitment domain 8 (CARD8) and PIDD1, and open questions that continue to challenge the field as we move toward greater understanding of this enigmatic signaling pathway.