RUNX1 is a core-binding factor transcription factor essential for definitive hematopoiesis 1. It functions as a sequence-specific DNA-binding transcription activator that regulates transcription by RNA polymerase II, controlling genes critical for myeloid differentiation and granulocyte development. Mechanistically, RUNX1 acts as a transcriptional activator that binds cis-regulatory DNA regions to promote expression of hematopoietic genes 1. In glioblastoma, RUNX1 stabilization by the deubiquitinase USP10 promotes mesenchymal phenotypes and metastatic properties 2. RUNX1 also interacts with NPM1 to facilitate FOSL2-mediated transcription of extracellular matrix genes, independent of its direct transcriptional function 3. In colorectal cancer, RUNX1 directly activates MUC13 transcription, which triggers Wnt/β-catenin signaling promoting proliferation and invasion 4. Clinically, germline RUNX1 mutations cause familial platelet disorder with associated myeloid malignancy (FPDMM), characterized by thrombocytopenia, defective platelet function, and leukemia risk 15. Somatic RUNX1 alterations are among the most frequent mutations in hematological malignancies, including acute myeloid leukemia, acute lymphoblastic leukemia, and myelodysplastic syndromes 16. RUNX1 mutations dysregulate target genes through promoter hypermethylation and target repression 6. RUNX1 functions as both an oncogene and tumor suppressor in solid tumors 7, with emerging therapeutic targeting strategies including small molecules and epigenetic therapies 8.