RUNX1T1 is a transcriptional corepressor that functions as a key component of the core-binding factor complex in hematopoiesis. The protein recruits histone deacetylases and other corepressors to DNA-binding transcription factors, blocking expression of genes essential for hematopoietic differentiation 1. In normal hematopoiesis, RUNX1T1 negatively regulates proliferation and differentiation of hematopoietic progenitors through histone modification 2. The pathogenic RUNX1-RUNX1T1 fusion protein, generated by t(8;21) translocation, is the most common recurrent abnormality in acute myeloid leukemia (AML) 3. This fusion disrupts normal core-binding factor function, recruiting transcriptional repressors that block hematopoietic gene expression while impairing apoptosis and promoting leukemic self-renewal 1. RUNX1-RUNX1T1 AML demonstrates a distinct mutational landscape, enriched in epigenetic regulators and showing particular vulnerability to CDK4/6 inhibition through CCND2 dependency 43. Beyond leukemia, RUNX1T1 exhibits broader roles in cell fate decisions, regulating neuronal differentiation, microglial activation, intestinal development, adipogenesis, and angiogenesis through alternative splicing 2. In glioblastoma, RUNX1T1 downregulation correlates with poor prognosis; restoring expression degrades HIF1α and reduces proliferation while enhancing chemotherapy sensitivity 5.