Emerging evidence reveals that protein palmitoylation critically modulates drug sensitivity, with PD-L1 hyperpalmitoylation driving cisplatin resistance in bladder cancer by stabilizing immune checkpoint signaling, while ZDHHC22-mediated palmitoylation overcomes endocrine resistance in ER-negative breast cancer via mTOR destabilization and AKT pathway suppression (24), establishing palmitoylation as both a predictive biomarker and therapeutic target for treatment-resistant malignancies. The gene discussed is ZDHHC22; the disease is urinary bladder cancer.