Immunity-related GTPase family M protein (IRGM)

Immunity-related GTPase family M protein (IRGM) is a GTP-binding protein and autophagy regulator encoded by the IRGM gene, playing a pivotal role in the regulation of selective autophagy (including xenophagy and mitophagy), immune responses to intracellular pathogens, and inflammation. IRGM triggers autophagy in cells infected with bacteria or viruses, thus protecting cells from infection and aiding in intracellular pathogen destruction[1][2][3][4][5]. It modulates innate immunity through interaction with autophagy and inflammasome proteins, helps maintain cellular homeostasis by regulating lysosomal biogenesis, and suppresses excessive inflammatory responses by negatively regulating the NLRP3 inflammasome and type I interferon signaling[1][4][5]. IRGM variants are associated with increased risk for Crohn’s disease and several other inflammatory, infectious, and autoimmune conditions. Dysregulation or genetic polymorphisms in IRGM can contribute to chronic inflammation, defective immune responses, and susceptibility to diseases such as tuberculosis, leprosy, Crohn’s disease, systemic lupus erythematosus, and certain cancers[1][3][4][5]. No approved drugs directly target IRGM, but it remains an important mechanistic target in research for inflammatory and infectious diseases.

Other names

IFI1IRGM1LRG-47LRG47LRG-47-like proteinimmunity-related GTPase family, Mimmunity-related GTPase family, M1interferon-inducible protein 1MGC149263MGC149264A1A4Y4_HUMAN

Autophagy induction, Negative regulation of inflammasome activation, Regulation of interferon responses, Promotion of lysosomal biogenesis