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Autophagy is at the intersection of metabolic, quality control, and anti-microbial processes and responds to a range of inputs such as starvation, cytoplasmic quality control tags, and microbial products.Although the organization of pre-autophagosomal structures in yeast have been well understood, the mammalian counterparts have not been fully delineated.In human cells,members of the superfamily of TRIM proteins organize core autophagy apparatus and link it with direct recognition of exogenous and endogenous autophagic targets.TRIMs function as regulators of autophagy, as receptors recognizing autophagic cargo, and as platforms for the assembly of the core autophagy regulators and effectors to initiate precision (highly selective)autophagy of targets such as the incoming HIV viral core or a variety of endogenous cellular substrates without causing collateral nonspecific degradation.A similar type of platform is provided by the human immunity-related GTPase, IRGM, a risk factor for Crohs disease (CD)and tuberculosis, with a hitherto unclear mechanism of action in autophagy regulation.We report that IRGM interacts with key autophagy regulators, ULK1, Beclin 1, and ATG16L1.We show that IRGM links this platform with microbial sensors by making molecular complexes with NOD2, another genetic risk factor in CD.The formation of NOD2-1RGM complex is stimulated in response to microbial products, whereas increased association of NOD2 with IRGM promotes IRGM-directed assembly of autophagy regulators.Thus, IRGM platform couples the core autophagic machinery with microbial sensors.In summary, several platform-forming devices have been identified as sites for organization of the core autophagy apparatus for precision recognition and removal of autophagic targets.