Highlights • NLRP3 Cys126 is palmitoylated by ZDHHC7 in macrophages • ZDHHC7-mediated NLRP3 Cys126 palmitoylation is critical for NLRP3 TGN localization • Cys126 palmitoylation is vital for recruiting ASC and inflammasome assembly • Cys126 palmitoylation promotes inflammasome activation in macrophages and in vivo Summary Nucleotide oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome hyperactivation contributes to many human chronic inflammatory diseases, and...