Using immortalized murine macrophages and Nlrp3-dependent cell death as a readout, Schmid-Burgk et al. described a genome-scale CRISPR screen, and pinpointed NEK7 as a critical player for NLRP3 inflammasome activation which underlies many metabolic diseases including atherosclerosis (Schmid-Burgk et al., 2016). Here, NLRP3 is linked to metabolic disease.