The serine/threonine kinases CK1 play numerous roles in development and signalling cascades, such as Wnt/β-catenin, as well as in tumour biology. It was previously assumed that CK1 kinases are constitutively active and do not require additional factors, although this has been challenged by the discovery of the DEAD box RNA helicase DDX3X that enhances the kinase reaction. To address the existence of a CK1–DDX3X interaction in vivo, Beat Suter and co-workers now (jcs207316) developed a Förster resonance energy transfer (FRET)-based sensor to monitor CK1 activity in cells. The authors find that DDX3X is required for full CK1 activity and that its biological functions are mutually exclusive: the kinase-activating phosphorylation of DDX3X by CK1 impairs the ATPase RNA helicase activity of DDX3X, whereas the addition of RNA diminishes binding of DDX3X to CK1. Further, the authors map potential interaction sites between CK1 and DDX3X, and identify peptides that interfere with CK1 activity. Importantly, mutations in DDX3X that had been identified in medulloblastoma patients increased the activity of CK1 in living cells. Aberrant stimulation of CK1-mediated pathways, such as Wnt/β-catenin and sonic hedgehog signalling, might thus be an underlying cause of medulloblastoma tumour formation, and the identified blocking peptides could provide a therapeutic option for such tumours.