Immunity-related GTPases (IRG) (also known as p47 GTPases) are a family of GTPase proteins found in vertebrates, which play critical roles in mediating innate resistance to intracellular pathogens. IRG genes have been found in a number of mammals and lower species including mice, rats, zebrafish and humans. Most of the mouse genes contain interferon-stimulated response elements which mediate transcriptional activation by IFNs. In humans, only two IRG genes have been found: human IRGC encodes a full-length IRG protein that, like the mouse homologue, is constitutively expressed in testis, while human IRGM encodes a considerably truncated protein that is constitutively expressed in cultured cells including some macrophage cell lines. As the two human genes IRGC and IRGM are not subject to IFN control, it has been suggested that the host resistance mechanism supported by IRG proteins in the mouse is lacking in humans.