The evidence now suggests that the generalized, IFNγ-dependent immunodeficiency caused by loss of Irgm1 is due to loss of one of the three essential regulator proteins of the IRG system, and probably results from the cytopathic effects of activated GKS subfamily IRG protein aggregates in the cytoplasm (Hunn et al., 2008; Papic et al., 2008; Henry et al., 2009a). Here, IFNG is linked to immunodeficiency disease.