ZDHHC9 is an X-linked palmitoyltransferase that catalyzes S-palmitoylation of diverse cellular proteins, playing critical roles in viral infection, cellular metabolism, and immune regulation. Mechanistically, ZDHHC9 palmitoylates target proteins at specific cysteine residues, with activity enhanced by reactive oxygen species (ROS) and facilitated by protein-protein interactions 1. In SARS-CoV-2 infection, ZDHHC9 works sequentially with ZDHHC20 to palmitoylate spike protein in the endoplasmic reticulum, protecting it from degradation and enabling viral fusion [UniProt]. ZDHHC9 also palmitoylates metabolic regulators: GLUT1 (cysteine 207) to maintain plasma membrane localization and promote glucose uptake in glioblastoma 2, and LDHA (cysteine 163) to enhance lactate production in pancreatic cancer 3. In innate immunity, ZDHHC9 palmitoylates gasdermin D (GSDMD, cysteine 191/192) to facilitate pyroptosis and inflammatory responses 41, and cGAS (cysteines 404/405) to activate the STING pathway 5. ZDHHC9 also palmitoylates Bip/GRP78 in bladder cancer, inhibiting the unfolded protein response 6. Disease relevance includes X-linked intellectual developmental disorder (syndromic, Raymond type) and oncogenic roles in multiple cancers where ZDHHC9 upregulation correlates with poor prognosis 263. ZDHHC9 emerges as a potential therapeutic target for cancer and infectious diseases.