ZDHHC1 (zinc finger DHHC-type containing 1) is a palmitoyltransferase that regulates protein S-palmitoylation and functions as a multifaceted cellular regulator. Beyond its canonical palmitoyltransferase activity, ZDHHC1 possesses palmitoyltransferase activity-independent functions in antiviral immunity 1. Mechanism: ZDHHC1 orchestrates multiple cellular processes through palmitoylation of diverse substrates. It promotes NLRP3 inflammasome activation by palmitoylating NLRP3 at two sites, facilitating its subcellular trafficking to the microtubule-organizing center and subsequent phosphorylation-dependent activation 2. ZDHHC1 palmitoylates IGF2BP1 to suppress colorectal cancer growth via LIPG downregulation 3, palmitoylates Gpm6a to maintain mammary stem cell activity 4, and palmitoylates GSDMD to enhance pyroptosis in prostate cancer 5. Additionally, ZDHHC1 palmitoylates p110α to regulate PI3K-Akt-mTOR signaling in atherosclerosis 6. Disease relevance: ZDHHC1 expression is frequently downregulated in various cancers including colorectal, prostate, and endometrial carcinomas, correlating with poor prognosis 357. DNA methylation silences ZDHHC1 in multiple tumor types 8. Zdhhc1 deficiency mitigates LPS-induced inflammation and atherosclerotic lesion formation 26. Clinical significance: ZDHHC1 functions as a tumor suppressor across multiple cancer types and represents a potential therapeutic target for cancer prevention and atherosclerosis intervention.