ZDHHC1 is a palmitoyltransferase that catalyzes S-palmitoylation of multiple substrates and functions as a critical regulator of inflammatory and immune signaling. Beyond its enzymatic activity, ZDHHC1 acts independently to activate STING1, promoting its oligomerization during innate immune responses to DNA viruses 1. The enzyme also orchestrates NLRP3 inflammasome activation by palmitoylating NLRP3 at two sites, enabling its trafficking from mitochondria and the trans-Golgi network to the microtubule-organizing center, where phosphorylation facilitates inflammasome assembly 2. Zdhhc1 knockout mice showed reduced LPS-induced inflammation and improved survival 2. In cancer contexts, ZDHHC1 acts as a tumor suppressor: it is frequently downregulated through promoter methylation across multiple malignancies, and restoration of expression inhibits cell proliferation and induces pyroptosis through oxidative and endoplasmic reticulum stress 3. In colorectal cancer, ZDHHC1 suppresses growth by palmitoylating IGF2BP1, which destabilizes LIPG mRNA in an m6A-dependent manner 4. ZDHHC1 also palmitoylates p53 at three cysteine residues, facilitating its nuclear translocation and tumor suppression; cancer cells evade this by hypermethylating ZDHHC1 5. In atherosclerosis, Zdhhc1 deficiency reduces foam cell formation and atherosclerotic plaque burden in ApoE−/− mice by decreasing p110α palmitoylation and suppressing PI3K-Akt-mTOR signaling 6. These findings position ZDHHC1 as a tumor suppressor and therapeutic target in cancer and cardiovascular disease.