Research over the past decade has revealed how NF-κB essential modulator (NEMO; 
also known as IKKγ) regulates the IKKα-IKKβ signalling axis in the innate immune 
system. The discovery that NEMO is a polyubiquitin-binding protein and that the 
IKK complex is modulated by other protein kinases that are themselves controlled 
by polyubiquitin chains has provided a deeper molecular understanding of the 
non-degradative roles of ubiquitylation. New mechanistic insights of NEMO and 
related polyubiquitin-binding proteins have become a paradigm for how the 
interplay between phosphorylation and ubiquitylation controls cell signalling 
networks in health and disease.