ZDHHC11 is a palmitoyltransferase that catalyzes S-acylation (palmitoylation) of multiple protein substrates to regulate diverse cellular processes. The enzyme modifies key metabolic proteins including ATGL, where palmitoylation at cysteine 15 is required for catalytic activity and lipid droplet homeostasis 1. ZDHHC11 also regulates autophagy by palmitoylating ATG2A at its C-terminus, anchoring it to the endoplasmic reticulum until depalmitoylation allows interaction with phagophores during starvation-induced autophagy 2. In oncology, ZDHHC11 promotes osimertinib resistance in EGFR-mutant lung cancer by palmitoylating AXL at Cys869, leading to constitutive PI3K-AKT signaling 3, while its knockdown reduces B-cell lymphoma growth 45. The enzyme demonstrates tissue-protective roles, alleviating chondrocyte senescence in osteoarthritis through APOD regulation 6. ZDHHC11 also functions in antiviral immunity, palmitoylating STING to enhance interferon responses against DNA viruses 7 and suppressing Zika virus infection by palmitoylating the viral envelope protein 8. These findings establish ZDHHC11 as a critical regulator of metabolism, cancer progression, tissue homeostasis, and antiviral defense through substrate-specific palmitoylation.