CK2: a different kind of kinase?

We tend to think of kinases as signalling molecules that are switched on in response to specific stimuli and phosphorylate a discrete set of effectors appropriate to the response required. But CK2 is different: the kinase is constitutively active with or without its non-catalytic β subunits, and it has >300 cellular substrates. So what exactly is its role? In a Commentary on p. 3873, Lorenzo Pinna discusses the apparent paradox of constitutive CK2 activity as well as evidence that it can in fact be regulated. CK2 can be considered as an independent executor whose activity is essential for the signalling network but is not normally adjustable. Recent work, however, indicates that CK2 is part of a pathway that inhibits RNA polymerase III activity when genome integrity is compromised. In this case, the β subunits target CK2 to TATA-binding protein but these interactions can be disrupted by DNA damage signalling. A similar mechanism could operate in the Wnt pathway; indeed,β-subunit-dependent targeting/docking might be a fundamental aspect of CK2 function.