The enzyme CDK8 and its paralog CDK19 are essential modules of the Mediator, a large protein complex that coordinates several key steps in transcription. CDK8 and CDK19 are highly similar and were thought to be functionally redundant. The group of Pavel Kovarik now discovered that CDK8/CDK19 are actually mechanistically distinct and activate different sets of genes in the interferon-induced anti-viral response. The results revise our understanding of anti-viral immunity and could help develop novel therapies of immune disorders. The findings are published in Molecular Cell.