We generated mice lacking all IKK subunits (IKKα, IKKβ, and NEMO) in parenchymal liver cells and compared the phenotype to mice lacking only the catalytic subunits IKKα and IKKβ to functionally assess the potential role of free NEMO molecules unbound to the catalytic subunits in the mediation of cholestasis and liver cancer. The gene discussed is IKBKB; the disease is cholestasis.