The oligomeric I kappa B kinase (IKK) is composed of three polypeptides:IKK[small alpha, Greek] and IKK[small beta, Greek], the catalytic subunits, and IKK[small gamma, Greek], a regulatory subunit. IKK[small alpha, Greek] and IKK[small beta, Greek] are similar in structure and thought to have similar function-phosphorylation of the I kappa B inhibitors in response to proinflammatory stimuli. Such phosphorylation leads to degradation of I kappa B and activation of nuclear factor kappa B transcription factors. The physiological function of these protein kinases was explored by analysis of IKK[small alpha, Greek]-deficient mice. IKK[small alpha, Greek] was not required for activation of IKK and degradation of I kappa B by proinflammatory stimuli. Instead, loss of IKK[small alpha, Greek] interfered with multiple morphogenetic events, including limb and skeletal patterning and proliferation and differentiation of epidermal keratinocytes.