The IKK kinase complex is the core element of the NF-κB cascade (see section of Axon Ligands™ interacting with NF-κB signaling). It is essentially made of two kinases (IKKα (or IKK-1) and IKKβ (or IKK-2); EC 2.7.11.10) and a regulatory subunit, NEMO/IKKγ. NF-κB represents a family of transcription factors that are normally kept inactive in the cytoplasm through interaction with inhibitory molecules of the IκB family. In response to multiple stimuli such as inflammatory cytokines, bacterial or viral products, or various types of stress, the IκB molecules become phosphorylated on two critical serine residues. This modification is recognized by a specific E3 ubiquitin ligase complex and undergoes polyubiquitination, which targets them for rapid degradation by the 26S proteasome. As a consequence, free NF-κB enters the nucleus and activates transcription of a variety of genes participating in the immune and inflammatory response, cell adhesion, growth control, and protection against apoptosis.