These severe on-target toxicities of IKKβ inhibitors have exposed the serious consequences of long-term IKK inhibition, which combined with the associated immunodeficiency and increased risks of malignancies arising from the liver, skin and other tissues [9,11,107,132,133,134], have irrevocably undermined any research efforts to clinically develop IKKβ-targeting therapeutics. This evidence concerns the gene IKBKB and Immunodeficiency.