The transcription factor NFκB is retained in the cytoplasm in an inactive form by the inhibitory protein IκB. Activation of NFκB requires that IκB be phosphorylated on specific serine residues, which results in targeted degradation of IκB. IκB kinase α (IKKα), previously designated CHUK, interacts with IκB-α and specifically phosphorylates IκB-α on the sites that trigger its degradation Serines 32 and 36. IKKα appears to be critical for NFκB activation in response to proinflammatory cytokines. Phosphorylation of IκB by IKKα is stimulated by the NFκB inducing kinase (NIK), which itself is a central regulator for NFκB activation in response to TNF and IL-1. The functional IKK complex contains three subunits, IKKα, IKKβ and IKKγ (also designated NEMO), and each appear to make essential contributions to IκB phosphorylation.