PIM3 is a serine/threonine kinase that functions as an oncogenic proto-oncogene with multiple roles in cell survival and proliferation 1. The kinase promotes cell survival through phosphorylation-mediated stabilization of regulatory proteins; specifically, PIM3 phosphorylates MLF2 at Ser65, enhancing its interaction with deubiquitinase USP21 and promoting osteosarcoma metastasis 2. PIM3 is frequently overexpressed in human cancers including hepatoblastoma, colorectal cancer, and osteosarcoma, where it correlates with advanced disease stage, lymph node metastasis, and poor prognosis 34. Functionally, PIM3 knockout suppresses tumorigenesis, inhibits cell-cycle progression, reduces cancer cell stemness, and increases apoptosis in hepatoblastoma cells 5. Paradoxically, endothelial PIM3 protects the vascular barrier during metastasis by maintaining junctional cadherin-5 and catenins; PIM inhibition increases vascular leakage and metastatic colonization 6. In multiple myeloma, PIM kinases including PIM3 regulate cell growth, apoptosis, and drug resistance, making them therapeutic targets 7. These findings position PIM3 as a critical oncogenic kinase in multiple malignancies and an emerging therapeutic target, though its protective role in the endothelial barrier warrants consideration for combination therapy strategies.