PA2G4 (proliferation-associated 2G4), also known as ErbB3-binding protein 1 (EBP1), is a multifunctional regulator with context-dependent roles in cellular homeostasis and disease. Structurally, PA2G4 exists as two isoforms—PA2G4-p42 and PA2G4-p48—that often exert opposing functions 1. Mechanistically, PA2G4 regulates transcription as an androgen receptor corepressor and E2F1 transcription inhibitor, while also binding RNA and participating in ribosomal RNA processing and translation 2. Beyond transcription, PA2G4 interacts with critical oncoproteins: it binds MYCN in neuroblastoma 3 and associates with presenilin in γ-secretase, inhibiting amyloid-β production 4. PA2G4 can function as either a tumor suppressor or oncogene depending on tissue context, with dysregulation linked to multiple cancers including neuroblastoma, glioblastoma, AML, and nasopharyngeal carcinoma 1567. Clinically, PA2G4 expression correlates with prognosis across diverse tumor types 1. Recent therapeutic approaches target the PA2G4-MYCN protein-protein interface with small molecule inhibitors 3, while PA2G4 shows promise as a target in 3q26 AML when combined with histone deacetylase inhibitors 5. Additionally, PA2G4 modulation affects cardiac regeneration through NF110-NF45 signaling 8, and EBP1 proteolysis contributes to Alzheimer's disease pathology 4.