EIF5A2 (eukaryotic translation initiation factor 5A2) is a translation elongation factor that promotes ribosome rescue during stalling, particularly at polyproline-containing sequences 1. Beyond its canonical role in translation, EIF5A2 functions as a multifaceted regulator of cellular processes including cell cycle progression, mRNA decay, and stress response. In cancer, EIF5A2 is frequently overexpressed through gene amplification or hypoxia-induced mechanisms and acts as an oncogene 2. The protein promotes tumor cell proliferation, epithelial-mesenchymal transition (EMT), and cancer stem cell properties 3. EIF5A2 overexpression is associated with increased metastasis, angiogenesis, and poor prognosis across multiple cancer types including hepatocellular carcinoma, esophageal squamous cell carcinoma, and oral cancer 425. Mechanistically, EIF5A2 activates oncogenic pathways such as PI3K/AKT/mTOR and HIF1α-mediated signaling, while downregulating pro-apoptotic factors like Bim 65. EIF5A2 also contributes to drug resistance and immune evasion by promoting M2-like tumor-associated macrophage polarization 3. Importantly, targeting EIF5A2 reverses chemoresistance and reduces invasion, making it a promising therapeutic target 75.