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