Increasing evidence suggests that citrullination is a key process involved in inflammatory disease and cancer. Our aim is to understand the role of citrullination by identifying key targets and decipher the role in the disease context. In previous studies we identified the master transcription factor E2F to be under citrullination control, and further clarified its impact on other post-translational modifications including methylation and acetylation. In recent studies, we have found that RNA splicing is influenced by PADs through the citrullination of RNA binding proteins and splicing factors, with important differences apparent in diseased compared to normal cells. Our results suggest that PADs have widespread effects on gene expression mediated at multiple levels. The evolving information on their biological roles has in turn fuelled significant interest in exploiting PADs as a therapeutic target in cancer.