Nuclear factor kappa B (NF-kappaB) is a ubiquitous transcription factor and an essential mediator of gene expression during activation of immune and inflammatory responses. NF-kappaB mediates the expression of a great variety of genes in response to extracellular stimuli. NF-kappaB is associated with IkappaB proteins in the cell cytoplasm, which inhibit NF-kappaB activity. The IkappaB kinase (IKKalpha and IKKbeta) phosphorylates IkB and mediates NF-kappaB activation. A novel molecule in the IKK complex was recently identified and termed IKKgamma/NEMO/FIP3/IKKAP1. IKKgamma interacts with IKKbeta and is required for the activation of IKK complex and NF-kappaB by LPS, PMA, TNF, and IL-1 stimulation. FIP3 was also shown to bind to RIP and NIK and to mediate TNF-induced NF-kappaB activation.