The nucleoskeleton is composed of many interacting structural proteins that provide the framework for DNA replication, transcription and a variety of other nuclear functions. For example, the type-V intermediate filament proteins, the lamins, and their associated proteins (e.g. Lap2alpha) play important roles in DNA replication and transcription. Furthermore, actin, actin-related proteins and other actin-associated proteins likewise appear to be important in nuclear functions because they are components of chromatin-remodeling complexes and are involved in mRNA synthesis, processing and transport. Newly described nuclear proteins that contain both actin- and lamin-binding domains could be involved in regulating molecular crosstalk between these two types of nucleoskeletal proteins. This range of activities might help to explain why genetic defects in some of the nucleoskeletal proteins contribute to an ever-expanding list of human diseases.