RUNX2 (Runt-related transcription factor 2) is a critical transcription factor essential for osteoblast differentiation and skeletal development 1. RUNX2 functions as a master regulator that induces the commitment of multipotent mesenchymal cells to osteoblast lineage cells and enhances osteoprogenitor proliferation 1. The protein is required for chondrocyte maturation and both intramembranous and endochondral ossification 1. RUNX2 promotes bone formation by inducing expression of major bone matrix protein genes including COL1A1, SPP1, IBSP, and BGLAP/osteocalcin 1. The transcription factor works in conjunction with cofactor CBFB, which enhances DNA-binding capacity and protein stability 1. Beyond its role in bone development, RUNX2 has emerged as an important factor in cancer progression, where it recruits repressive complexes to regulate genes involved in cell growth and metastasis 2. RUNX2 also contributes to immune function by promoting differentiation of cytotoxic tissue-resident memory T cells 3. Clinical relevance includes mutations causing cleidocranial dysplasia and metaphyseal dysplasia, while altered RUNX2 expression is associated with ankylosing spondylitis and osteoporosis 45. Therapeutic targeting of RUNX2 pathways shows promise for treating bone disorders and certain cancers.