Filamin A (FLNA), an actin-binding protein, interacts with a wide range of proteins with great functional diversity. Previous studies have demonstrated that FLNA can regulate transcription factor activity. The mammalian Runx family of transcription factors, Runx1, Runx2 and Runx3 have essential roles in development and disease. In order to regulate transcription the Runx proteins form obligate dimers with a co-regulator, CBFÎ². Previous studies have shown that CBFÎ² interacts with FLNA. In addition, FLNA has been shown to interact directly with Runx2 to supress Runx2-mediated transcription. However, to date the precise nature of the interaction between Runx2 and FLNA has not been determined. The aim of this study was therefore to determine the minimal domains on Runx2 and FLNA that mediate the interaction and subsequently determine the structural basis of the interaction using Nuclear Magnetic Resonance (NMR) spectroscopy. Understanding the structural basis of this interaction may be important in the design of therapeutic reagents to modify Runx function in human disease. A series of Runx2 and FLNA polypeptides were generated and the minimal regions required to interact with each other was determined using GST pulldown assays. It was established that the interaction between Runx2 and FLNA is mediated primarily by Ig domain 23 of FLNA and a short region on Runx2 known as the Nuclear Matrix Targeting Sequence (NMTS). NMR was subsequently used to investigate how FLNA interacts with Runx2, and confirmed that domain 23 of FLNA is responsible for the interaction with the NMTS domain of Runx2. A partial region of the NMTS was resolved using backbone NMR assignment. A two-mode interaction was discovered through chemical shift differences between domain 23 and NMTS. These findings reveal a novel interaction between domain 23 in FLNA and NMTS domain in Runx2. Experiments were also performed on mutant forms of CBFÎ² found in patients with breast cancer. The impact of these mutations on CBFÎ² structure and function has not been previously characterised. Nine CBFÎ² missense mutations were expressed and purified and their ability to interact with the Runt domain of Runx1 was analysed by GST pulldown and electrophoretic mobility shift assays. The mutations affected the formation of the CBFÎ²/Runt complex either by disrupting the interface or by affecting the stability of the protein.