Transcription factor RUNX1 is one of the key regulatory proteins in vertebrates. RUNX1 controls hematopoiesis and angiogenesis and is indispensable for the emergence of sites of definitive hematopoiesis during embryogenesis and for blood stem cells differentiation in adult bone marrow. The RUNX1 gene is a frequent target of chromosomal translocations causing acute leukemias. Many human leukemias are somehow associated with RUNX1 mutations. Nevertheless, the precise mechanism guiding the tissue-specific manner of RUNX1 expression remains unknown. The review summarizes the experimental data accumulated over the past twenty years, beginning from the date of the first annotation of the RUNX1 cDNA sequence. The structure, isoforms, covalent modifications, and role in various regulatory cascades are considered for the RUNX1 transcription factor, as well as the RUNX1expression regulation, mutations, and the involvement in chromosomal translocations.