EIF2S2 (eukaryotic translation initiation factor 2 subunit beta) is a core component of the eIF2 heterotrimer complex essential for protein synthesis initiation. It functions by forming a ternary complex with GTP and initiator tRNA, which binds to the 40S ribosomal subunit to form the 43S pre-initiation complex 1. Following mRNA binding and 60S subunit joining, GTP hydrolysis releases eIF2-GDP, which recycles through eIF2B-catalyzed GDP-GTP exchange to enable successive rounds of translation initiation. Beyond its canonical translational role, EIF2S2 exhibits oncogenic functions across multiple cancer types. High EIF2S2 expression correlates with poor prognosis in hepatocellular carcinoma, glioblastoma, gastric cancer, breast cancer, oral squamous cell carcinoma, and cervical cancer 234567. EIF2S2 promotes tumorigenesis through multiple mechanisms: it stabilizes MYC protein via LINC01600 interaction to activate Wnt/β-catenin signaling 8, transcriptionally upregulates HIF1α to activate PI3K/AKT/mTOR pathways 4, and inhibits TGF-β/SMAD4-mediated tumor suppression 7. Additionally, elevated EIF2S2 expression correlates with reduced immune cell infiltration and checkpoint blockade resistance 96, suggesting EIF2S2 modulates immune evasion. These findings establish EIF2S2 as a potential prognostic biomarker and therapeutic target in cancer.