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Many receptors signal via adaptors to the IKK-NF-κB axis, transducing extracellular cues to transcriptional regulation. In this issue, Meng et al. (2015. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201505091) reveal that the IKK regulator NLRC5 shapes NF-κB activity through a feedforward loop of NLRC5 ubiquitination and deubiquitination, highlighting a new pathway modulating IKK-NF-κB activity.

A feedforward loop of NLRC5 (de)ubiquitination keeps IKK–NF-κB in check