GFI1 is a transcriptional repressor essential for hematopoiesis that functions in a cell-context and development-specific manner 1. It binds to specific DNA sequences (5'-TAAATCAC[AT]GCA-3') in gene promoters and recruits histone deacetylase complexes (EHMT2-GFI1-HDAC1, AJUBA-GFI1-HDAC1, and RCOR-GFI-KDM1A-HDAC) to suppress genes involved in multilineage blood cell development 2. GFI1 regulates neutrophil differentiation, promotes lymphoid cell proliferation, and is required for granulocyte development while inhibiting macrophage differentiation 3. Beyond transcriptional roles, GFI1 acts as a substrate adapter for PRMT1 in DNA damage responses, facilitating methylation of TP53BP1 and MRE11 4. Additionally, GFI1 regulates toll-like receptor inflammatory responses by antagonizing RELA 5. Loss-of-function GFI1 mutations cause severe congenital neutropenia and dominant nonimmune chr1 idiopathic neutropenia 67, while the GFI1-36N variant increases AML chr1 aberrations and impairs homologous recombination DNA repair, sensitizing leukemic cells to combination DNA-damaging therapies 8. Conversely, enforced GFI1 expression impedes leukemic cell growth and promotes myeloid differentiation 9. GFI1 also regulates T cell differentiation, governing both terminally exhausted and tissue-resident memory T cell states 10, and elevated GFI1 in obesity-associated macrophages suppresses ACOD1 expression, exacerbating lipopolysaccharide-induced lung injury 11.