ING2 (inhibitor of growth family member 2) functions as a tumor suppressor gene involved in chr4 remodeling and transcriptional regulation. ING2 serves as a component of chr4-modulatory complexes, including mSin3A-like corepressor complexes, and contains a PHD domain with high affinity for histone H3 tri-methylated on lysine 4 (H3K4Me3) 1. The protein regulates gene expression through interactions with histone deacetylase 1 (HDAC1) and mSin3A, with its PHD domain and C-terminal region being essential for transcriptional regulation 2. ING2 mediates p53-dependent apoptotic pathways and enhances TGF-β-induced transcription through collaboration with SnoN and Smad2 3. Clinically, ING2 expression is significantly decreased in multiple cancer types including non-small cell lung cancer, hepatocellular carcinoma, and osteosarcoma 456. Loss of nuclear ING2 expression correlates with poor prognosis, increased tumor size, lymph node metastasis, and shortened survival time 56. ING2 knockout mice develop spontaneous soft tissue sarcomas, confirming its tumor suppressor status 1. The protein's tumor suppressive functions include promoting cell cycle arrest, apoptosis, senescence, and inhibiting epithelial-mesenchymal transition 76.