BZW2 (basic leucine zipper and W2 domains 2) is a translation initiation regulator that represses non-AUG and repeat-associated non-AUG (RAN) initiated translation by competitively inhibiting eukaryotic translation initiation factor 5 (EIF5) function 12. It increases translation initiation accuracy by impeding EIF5-dependent translation from non-AUG codons through interaction with EIF2S2 within the 43S pre-initiation complex 3. BZW2 functions as an oncogene across multiple cancer types. Elevated BZW2 expression is associated with poor prognosis in cervical cancer, colorectal cancer, hepatocellular carcinoma, and non-small cell lung cancer 4567. BZW2 promotes cancer progression by enhancing cell proliferation, invasion, and metastasis while suppressing apoptosis 45. Mechanistically, BZW2 activates oncogenic signaling pathways including Wnt/β-catenin and PI3K/AKT/mTOR 85. In nasopharyngeal carcinoma, TEAD4 transcriptionally activates BZW2 to promote AKT pathway activation and tumor progression 9. Clinically, BZW2 represents a promising therapeutic target. FDA-approved EZH2 inhibitors can indirectly suppress BZW2 expression as a potential colorectal cancer treatment strategy 5.