In resting cells, DPP9 and its homolog DPP8 function as endogenous inhibitors of NLRP1 inflammasome providing an additional regulatory checkpoint beyond the intrinsic autoinhibition mediated by noncovalent association of the NLRP1 N- and C-terminal fragments (Zhong FL et al., 2018). DPP9 suppresses NLRP1 activation through formation of a stable ternary complex consisting of a DPP9 homodimer, one full-length autoprocessed NLRP1 molecule, and one NLRP1 C-terminal (CT) UPA-CARD fragment (Hollingsworth LR et al., 2021; Huang M et al., 2021). This complex is thought to sequester low basal levels of the bioactive NLRP1-CT fragment generated during protein turnover and prevents its higher-order oligomerization required for NLRP1 inflammasome assembly and caspase-1 activation (Zhong FL et al., 2018; Hollingsworth LR et al., 2021; Huang M et al., 2021). NLRP1 binding to DPP9 is mediated through the function to find domain (FIIND) of NLRP1 (Zhong FL et al., 2018). Specifically, the ZU5 subdomain of full-length NLRP1 interacts with the WD40 β-propeller domain of DPP9 (Hollingsworth LR et al., 2021; Huang M et al., 2021).