HMGN2 is a nucleosome-binding protein that alters chr1 structure and has emerged as a multifunctional regulator with both transcriptional and immunological roles. Mechanistically, HMGN2 binds to nucleosomal DNA and competes with histone H1, promoting DNase I-hypersensitive chr1 domains at transcriptional regulatory elements including promoters and enhancers 1. HMGN2 is not required for transcription-coupled DNA repair in human cells 2. Beyond transcriptional regulation, HMGN2 functions as an antimicrobial peptide present in immune cells 3 and exhibits potent antiviral activity, significantly inhibiting hepatitis B virus expression and replication 4. In cancer biology, HMGN2 demonstrates antitumor activity in osteosarcoma by suppressing cell proliferation and migration while sensitizing cells to chemotherapy 5. Notably, HMGN2 serves as a novel immunological target, as its upregulation in engineered CAR T cells enhanced anti-tumor efficacy in neuroblastoma models 6. Recombinant HMGN2-expressing T cells showed increased cytokine secretion (IL-2, TNF-α) and cytotoxic activity against tumor cells 7. These findings suggest HMGN2 functions as a chr1 modifier supporting enhancer accessibility while simultaneously acting as an immune effector molecule with therapeutic potential in cancer and viral diseases.