EIF5A2 is a translation elongation factor that contains the post-translational modification hypusine and promotes efficient translation of polyproline-containing peptides and other ribosome-stalling motifs. As a ribosome quality control cofactor, it facilitates peptidyl transfer during CAT tailing steps. In normal tissues, EIF5A2 expression is limited primarily to testis and brain, with weak ubiquitous expression, contrasting with the ubiquitous distribution of its isoform EIF5A1. EIF5A2 is frequently overexpressed in multiple solid tumors through gene amplification or hypoxia-driven upregulation. In esophageal squamous cell carcinoma, increased EIF5A2 associates with metastasis, lymph node involvement, and shorter survival, operating via hypoxia-inducible factor-1α (HIF1α) signaling to promote epithelial-mesenchymal transition and angiogenesis 1. Elevated expression also correlates with poor prognosis in head and neck squamous cell carcinoma, brain lower-grade glioma, and hepatocellular carcinoma 2. EIF5A2 overexpression drives anchorage-independent growth and tumor formation in ovarian and intrahepatic cholangiocarcinoma models 3 4, activating PI3K/AKT/mTOR signaling and upregulating cell cycle and matrix metalloproteinase genes. Clinically, EIF5A2 inhibition via blocking hypusination using GC-7 reduced oral cancer cell proliferation and chemoresistance 5, while EIF5A2 knockdown enhanced sensitivity to cisplatin, crizotinib, and gemcitabine in hepatocellular carcinoma 2. These findings position EIF5A2 as both a prognostic biomarker and therapeutic target in cancer.