CDK8 (cyclin-dependent kinase 8) is a serine/threonine kinase that plays a crucial role in regulating DNA transcription and cell cycle progression. It forms a module with Cyclin C (CCNC), Med12, and Med13, which associates with the Mediator complex to modulate gene transcription. CDK8 phosphorylates the C-terminal domain of RNA polymerase II, influencing transcriptional elongation. In cancer, CDK8 acts as a positive regulator of oncogene-induced proliferation by recruiting pTEF-B and BRD4 to oncogenic genes, promoting efficient transcriptional elongation. However, it can also inhibit Mediator-dependent super-enhancer driven transcription in acute myeloid leukemia (AML), suggesting its role may vary depending on the oncogenic context. Additionally, CDK8 is often amplified in colorectal cancer, where it modulates beta-catenin activity, contributing to tumor progression.