NACC1 is a BTB/POZ domain-containing transcriptional co-regulator that functions as a transcriptional repressor in neuronal and cancer cells 1. It forms homo- or hetero-dimeric complexes through its BTB/POZ domain and regulates downstream signaling through transcriptional repression mechanisms 1. NACC1 is SUMOylated at conserved lysine residues and recruited to promyelocytic leukemia nuclear bodies, facilitating its regulatory functions 2. In cancer biology, NACC1 is substantially overexpressed across multiple tumor types and promotes tumor progression, cell proliferation, and survival 1. Mechanistically, NACC1 drives cancer pathways including the ADAM9/PI3K/AKT axis in acute myeloid leukemia and the CD44-JAK1-STAT3 axis in triple-negative breast cancer 34. NACC1 also maintains cancer stem cell stemness and suppresses anti-tumor immunity through myeloid-derived suppressor cell regulation 4. In neural function, a de novo R298W mutation impairs glutamatergic neurotransmission through altered binding to SynGAP1 and GluK2A, and elevated SUMOylation, causing intellectual disability and epilepsy 5. Clinically, NACC1 fusions (NIPBL::NACC1) characterize a distinct hepatic carcinoma subtype, and NACC1 inhibition phenocopies therapeutic benefit in melanoma immunotherapy contexts 67.