Alternatively, leveraging PYK2-specific regulatory mechanisms—such as its unique activation by Ca2+/PKC and oxidative stress (27, 29), and non-redundant nuclear scaffolding functions (e.g., β-catenin Y654 phosphorylation driving Wnt in PDAC; YAP/TAZ complex assembly sustaining cancer stemness) (18, 34) (18, 35)—enables context-selective targeting. The gene discussed is PTK2B; the disease is cancer.