Nuclear transcription factors of the NF-κB/Rel family are inhibited by IκB proteins, which inactivate NF-κB by trapping it in the cell cytoplasm. Phosphorylation of IκBs marks them out for destruction, thereby relieving their inhibitory effect on NF-κB. A cytokine-activated protein kinase complex, IKK (for IκB kinase), has now been purified that phosphorylates IκBs on the sites that trigger their degradation. A component of IKK was molecularly cloned and identified as a serine kinase. IKK turns out to be the long-sought-after protein kinase that mediates the critical regulatory step in NF-κB activation.