The canonical NF-κB pathway plays a major role in innate and adaptive immunity, and is triggered by many stimuli including proinflammatory cytokines (for example, TNF, IL-1), antigens, RANKL, and TLR ligands. NF-κB signalling initiated by different receptors requires the formation of proximal protein-protein interactions that are often receptor specific, but ultimately converge in the activation of the IκB kinase (IKK) complex, which mediates phosphorylation of the inhibitory IκB protein leading to its K48-polyubiquitination and degradation by the proteasome [20]. The IKK complex is comprised of the two catalytic subunits IKK1 and IKK2 (also known as IKKα and IKKβ) and the regulatory subunit NF-κB essential modulator (NEMO - also known as IKKγ) (Figure 1). Gene targeting experiments showed that IKK2 and NEMO, but not IKK1, are required for canonical NF-κB activation [21].