ZNF280B is a zinc finger transcription factor that functions as a DNA-binding protein regulating RNA polymerase II-dependent transcription 1. Mechanistically, ZNF280B suppresses p53 expression through multiple pathways. In prostate cancer, ZNF280B upregulates Mdm2 expression via the Mdm2 promoter, which promotes p53 nuclear export and subsequent proteasomal degradation 2. In lung cancer, extracellular vesicles derived from lung cancer stem cells transfer ZNF280B into recipient cells, similarly inhibiting p53 expression and promoting cancer cell proliferation, migration, and invasion 1. ZNF280B has substantial clinical relevance across multiple malignancies. It is frequently deleted in chr22 lymphocytic leukemia (15% of cases), with ZNF280B mRNA significantly reduced in 22q11 deletion cases 3. In adult T-cell leukemia/lymphoma, miR-342-3p-ZNF280B interactions are identified as diagnostic biomarkers for the chr22 ATLL subtype 4. Additionally, ZNF280B deletions occur in canine diffuse large B-cell lymphoma on chromosome 22, indicating conserved oncogenic relevance 5. The ZNF280B/p53 axis represents a key mechanism of cancer progression, with therapeutic implications for p53-pathway-based interventions.