EAPP (E2F-associated phosphoprotein) is a nuclear phosphoprotein that modulates E2F-dependent transcription and serves as a critical regulator of cell cycle progression and apoptosis 1. EAPP interacts with activating E2F family members (E2F-1, E2F-2, E2F-3) to enhance transcription of S-phase genes, promoting cell cycle entry 12. Mechanistically, EAPP binds to the p21 promoter and facilitates transcription initiation complex assembly, inducing p21 expression in both p53-dependent and p53-independent manners 2. EAPP also represses p14(ARF) expression and modulates Chk2 phosphorylation status, affecting DNA damage checkpoint control 13. Elevated EAPP levels—observed in most transformed cells—confer resistance to DNA damage-induced apoptosis through p21-dependent G1 arrest, while paradoxically increasing genomic instability and aneuploidy 23. EAPP overexpression stimulates MDR1 promoter activity, contributing to multidrug resistance in cancer cells 4. Conversely, EAPP knockdown impairs stress responses and triggers apoptosis, indicating that optimal EAPP levels are essential for cellular homeostasis 2. EAPP expression is regulated by GC-box binding proteins (Sp1, Sp3, Egr-1) at its TATA-less promoter 5. These properties position EAPP as a key mediator of transformation and potential therapeutic target in cancer.