ZDHHC17 is a palmitoyltransferase that catalyzes the addition of palmitate and other fatty acids onto various protein substrates, playing critical roles in cellular signaling and disease pathogenesis. The enzyme palmitoylates key neuronal proteins including SNAP25, DLG4/PSD95, and HTT, as well as SNAP23 in cytotoxic lymphocytes to facilitate regulated exocytosis 1. ZDHHC17 demonstrates broad substrate specificity, modifying proteins involved in diverse cellular processes including AKT activation through palmitoylation at specific cysteine residues, which promotes liver tumorigenesis in high-fat diet conditions 2. In cancer contexts, ZDHHC17 palmitoylates Oct4A to prevent lysosomal degradation and maintain glioblastoma stem cell characteristics 3, and activates JNK/p38 MAPK signaling pathways by interacting with MAP2K4 to drive glioblastoma progression 4. The enzyme also regulates inflammatory responses by palmitoylating NLRP3 at Cys419, enhancing inflammasome activation and contributing to inflammatory bowel disease development 5. Additionally, ZDHHC17 is involved in Golgi turnover through CALCOCO1-mediated selective autophagy 6 and modulates pyroptosis by palmitoylating the GSDME-C domain, contributing to chemoresistance in colorectal cancer 7. These diverse functions establish ZDHHC17 as a critical regulator of cellular homeostasis and a potential therapeutic target for multiple diseases.