Myosins are well characterised cytoskeletal proteins but a subset also exists within the nucleus. Here we focus on myosin VI, a protein which is regulated by an array of partner proteins that relate to functions ranging from endocytosis, autophagy and cellular homeostasis. Myosin VI is present in the nucleus and contributes to gene expression, DNA damage response and chromosome organisation. With regard to transcription, using a combination of super resolution imaging and 3D single molecule tracking we will show how myosin VI can support transcription hub formation. The hubs bring together several genes and multiple RNA Polymerase molecules to enable simultaneous gene expression. For the DNA damage response, we will reveal how myosin VI contributes to DNA damage signalling following treatment with cancer therapeutics. We will also explore how chromosome rearrangements occur during these processes. Overall, there are multiple nuclear functions of myosin VI, similar to its diverse activity in the cytoplasm. Myosin VI has roles in cancer and neurodegeneration, further studies will reveal if the nuclear activity contributes to disease.