Immunity-related GTPase family M protein 1 belongs to the p47 family of immunity related guanosine triphosphatases that regulate innate immune responses to intracellular pathogens. Research studies indicate that IRGM plays a role in autophagy during clearance of intracellular bacteria. Expression of IRGM in mice, but not in humans, is induced by inflammatory signals that include interferon and LPS. Polymorphisms in the corresponding IRGM gene are associated with some cases of tuberculosis, Crohn’s disease, and severe sepsis. Additional studies indicate that IRGM functions through regulation of autophagy. Mitochondrial IRGM plays a role in mitochondrial fission, membrane polarization, and mitophagy. Knockout mice for IRGM show increased susceptibility to infection as well as intestinal inflammation and Paneth cell abnormalities. Knockout mice against IRGM are also resistant to neuronal autophagy following stroke. RNA viruses commonly target IRGM in order to suppress autophagy and enhance infection.
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