PKN2 (protein kinase N2) is a serine/threonine protein kinase that functions as a Rho GTPase effector with diverse roles in cellular regulation and disease processes 1. The protein exhibits context-dependent functions in cancer, acting as both a tumor suppressor and promoter depending on the cellular environment. In colon cancer, PKN2 functions as a tumor suppressor by inhibiting M2 macrophage polarization through the DUSP6-Erk1/2 pathway and suppressing angiogenesis via HIF-1α regulation 23. However, in pancreatic cancer, PKN2 promotes myofibroblast differentiation in pancreatic stellate cells, and its loss paradoxically increases tumor invasion 4. PKN2 serves as a critical dependency for mesenchymal-like cancer cells, functioning through a PKN2-SAV1-TAZ signaling mechanism within the Hippo pathway 5. In vascular biology, PKN2 mediates flow-induced endothelial nitric oxide synthase activation through mechanosensitive Piezo1 channels, directly phosphorylating eNOS and regulating vascular tone and blood pressure 6. Additionally, PKN2 enhances immunosuppressive activity of myeloid-derived suppressor cells by promoting fatty acid oxidation through STAT3-CPT1B signaling 7. The kinase undergoes allosteric regulation through interactions with PDK1 and can be modulated by small molecule compounds targeting its PIF-pocket 8.