Eukaryotic transcription regulation is essential for cellular responses to diverse signals and for maintaining accurate gene expression patterns. Among regulatory mechanisms, post-translational modifications (PTMs) are pivotal in fine-tuning the activity of the transcriptional machinery and chromatin structure. Understanding how PTMs influence transcriptional regulation is key to decoding cellular function and the molecular underpinnings of cancer progression. Protein citrullination, a PTM involving the conversion of arginine to citrulline by the enzyme family peptidyl arginine deiminases (PADIs), plays a significant role in transcriptional dynamics. We showed that PADI2 specifically citrullinates the RNAPII to dictate the active transcription required to maintain cell proliferation in breast cancer. Functionally, Cit1810 enhances the association of active RNAP2 with the positive transcription elongation factor-b kinase complex. In this way, Cit1810 promotes the transcription regulation of essential genes contributing to oncogenesis. Our finding provides a new spectrum for the functional implication of citrullination on the transcription machinery in cancer. I will also share unpublished data on the broader role of PADI2-driven citrullination in transcriptional regulation.