The centrosomal hub unifies regulatory factors of NLRP3 inflammasome activation

The NLRP3 inflammasome is central to host defense and sterile inflammation and forms condensates at the microtubule-organizing center (also known as the centrosome), although the mechanisms regulating this process remain unclear. Here we define a functional relationship among microtubule transport, the centrosomal kinase NEK7, priming, and NLRP3 abundance. We show that microtubule-dependent transport is required for NEK7-dependent NLRP3 activation and promotes NEK7 to the pericentriolar material (PCM). Microtubules, priming, and NEK7 synergistically converge on PCM abundance, thereby creating a permissive centrosomal environment for NLRP3 condensation and inflammasome assembly. Elevated NLRP3 expression compensates for limited PCM abundance, rendering K⁺ efflux-induced activation independent of both NEK7 and priming in human and mouse macrophages. By contrast, NLRP3 overexpression only partially bypasses NEK7 dependence in response to the K⁺ efflux-independent stimulus imiquimod, likely due to its activation of a non-trans-Golgi network pool of NLRP3 that is quantitatively limited. Together, these findings define a conserved spatial mechanism in which microtubule transport, NEK7 localization, priming, and NLRP3 abundance integrate at the PCM to establish the activation threshold and magnitude of NLRP3 inflammasome signaling across species and stimuli.