CDK19 (cyclin dependent kinase 19) is a cyclin-dependent kinase that functions as part of the Mediator kinase module, regulating RNA polymerase II-mediated transcription 1. CDK19 and its paralog CDK8 are incorporated mutually exclusively into a 4-protein complex (including CCNC, MED12, and MED13) that reversibly associates with the 26-subunit Mediator complex 12. The kinase affects transcription indirectly through phosphorylation of transcription factors and by controlling Mediator structure and function 2. CDK19 promotes signal-induced transcriptional reprogramming, with inhibition reducing induction of signal-responsive genes following serum, NFκB, or protein kinase C stimulation 3. Beyond nuclear functions, CDK19 has cytoplasmic roles in mitochondrial dynamics, promoting mitochondrial fission through Drp1 phosphorylation at S616 4. CDK19 also facilitates RNA polymerase II ser2 phosphorylation through interaction with CYCLINL1 and the long non-coding RNA NEAT1-1 5. In prostate aging, CDK19 sequesters p53 to suppress p21 transcription, with age-related downregulation leading to cellular senescence 6. Dysregulation of CDK19 and other Mediator kinase module components has been implicated in intellectual disability and developmental disorders 7, highlighting its critical role in neurological development and cellular homeostasis.