ZDHHC22 is a palmitoyltransferase that catalyzes the addition of palmitate to cysteine residues on target proteins, regulating their stability, localization, and function. ZDHHC22 mediates palmitoylation of multiple substrates including the calcium-activated potassium channel KCNMA1, which is essential for its cell surface expression 1, and CCN3, where palmitoylation at cysteine 241 is required for proper secretion 2. Recent evidence demonstrates ZDHHC22 palmitoylates SMAD4 at cysteine 363, enhancing protein stability and transcriptional activity in pancreatic cancer 3. In breast cancer, ZDHHC22 expression is reduced in estrogen receptor-negative tumors and correlates with improved prognosis; mechanistically, ZDHHC22 suppresses mTOR signaling through palmitoylation-mediated destabilization, inhibiting cancer proliferation and restoring endocrine therapy sensitivity 4. ZDHHC22 expression is dysregulated in Alzheimer's disease and correlates with immune cell infiltration, suggesting roles in neurodegeneration 5. During influenza infection, the viral NS1 protein upregulates ZDHHC22 expression, and the enzyme modulates palmitoylation of host proteins involved in viral replication 6. ZDHHC22 emerges as a potential diagnostic and therapeutic target across multiple disease contexts.