ZDHHC8 encodes a palmitoyltransferase that catalyzes S-palmitoylation of multiple protein substrates, playing critical roles in cellular signaling and disease pathogenesis. The enzyme primarily functions by adding palmitate groups to cysteine residues of target proteins, affecting their stability, localization, and function 12. Key substrates include GPX4, which ZDHHC8 palmitoylates at Cys75 to enhance ferroptosis resistance in cancer cells 1, and SLC7A11, palmitoylated at Cys327 to promote protein stability and glioblastoma survival 2. In the nervous system, ZDHHC8 regulates AMPA receptor trafficking and glutamatergic neurotransmission, with overexpression increasing seizure susceptibility in epilepsy models 3. The gene has been investigated as a schizophrenia susceptibility candidate due to its location in the 22q11.2 deletion syndrome region, though meta-analyses show inconsistent associations 45. Clinically, ZDHHC8 expression correlates with cancer survival and represents a potential therapeutic target, as inhibition can enhance CD8+ T cell-mediated tumor ferroptosis 1. The enzyme's diverse substrate specificity and tissue-specific expression patterns suggest broad physiological importance in cellular homeostasis and disease processes.