ING4 (inhibitor of growth family member 4) functions as a multifaceted tumor suppressor through epigenetic and transcriptional mechanisms. As a component of HBO1 histone acetyltransferase complexes, ING4 mediates acetylation of histone H3 at lysine-14 (H3K14ac) and functions as an epigenetic reader of H3K4me3 histone marks, regulating chr12 structure and facilitating DNA replication 12. Through these chr12 modifications, ING4 modulates transcription of genes controlling cell proliferation and apoptosis 34. ING4 suppresses multiple hallmark cancer processes: pathologic cell cycle arrest, apoptosis, autophagy, contact inhibition, and hypoxic adaptation 5. It specifically inhibits tumor angiogenesis by suppressing Sp1 expression and downstream pro-angiogenic genes (MMP-2, COX-2) 6, and represses HIF activity through interaction with prolyl hydroxylase EGLN1 7. ING4 also cooperates with p53 to enhance acetylation and transcriptional activity of p53, amplifying apoptotic responses 8. Clinically, ING4 is frequently downregulated or deleted across multiple cancer types including colorectal, breast, gastric, and hepatocellular carcinomas 695. Reduced ING4 expression correlates with lymph node metastasis, advanced disease, and poor prognosis, making it a valuable prognostic biomarker 62. ING4 restoration via gene therapy shows promising antitumor efficacy, particularly when combined with other tumor suppressors 108.