ZDHHC12 is a palmitoyltransferase that catalyzes the addition of palmitate to cysteine residues on protein substrates, regulating critical immune and cellular processes 1. In antiviral immunity, ZDHHC12 palmitoylates MAVS at cysteine 79, acting as a checkpoint for MAVS aggregation and subsequent type I interferon production upon viral infection 2. Zdhhc12-deficient mice show severe susceptibility to lethal viral infection, highlighting its essential role in antiviral defense. In inflammation regulation, ZDHHC12 negatively regulates NLRP3 inflammasome activation by catalyzing NLRP3 palmitoylation, which promotes its degradation through chaperone-mediated autophagy (CMA), thereby suppressing excessive inflammation 134. Conversely, gain-of-function NLRP3 variants associated with autoinflammatory diseases show decreased palmitoylation and impaired CMA-mediated degradation. Beyond immunity, ZDHHC12 palmitoylates HDAC8 to promote hepatocellular carcinoma progression under high saturated fatty acid conditions 5, while its inhibition sensitizes ovarian cancer cells to cisplatin through ROS-mediated mechanisms 6. These multifaceted roles establish ZDHHC12 as a promising therapeutic target for inflammatory, autoimmune, viral, and malignant diseases.