IKK-γ is the regulatory subunit of the IKK core complex which phosphorylates inhibitors of NF-κB, thus leading to the dissociation of the inhibitor/NF-κB complex and ultimately the degradation of the inhibitor. Its binding to scaffolding polyubiquitin seems to play a role in IKK activation by multiple signaling receptor pathways. IKK-γ is also considered to be a mediator for TAX activation of NF-κB and it could be implicated in NF-κB-mediated protection from cytokine toxicity. It is essential for viral activation of IRF3 and is involved in TLR3- and IFIH1-mediated antiviral innate response.