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Recent studies highlight the importance of the host genome and microflora interactions in the pathogenesis of mucosal inflammation including IBD. Specifically, genome\u2010wide (GWAS) and also next\u2010generation sequencing (NGS)\u2014including whole exome or genome sequencing\u2014have uncovered a large number of susceptibility loci that predispose to autoimmune diseases and\/or the two phenotypes of IBD. In addition, the generation of \u201cIBD\u2010prone\u201d animal models using both reverse and forward genetic approaches has not only helped confirm the identification of susceptibility loci but also shed critical insight into the underlying molecular and cellular pathways that drive colitis development. In this review, we summarize recent findings derived from studies involving a novel early\u2010onset model of colitis as it develops in GTPase of immunity\u2010associated protein 5\u2010 (<jats:italic>Gimap5-<\/jats:italic>) deficient mice. In humans, <jats:italic>GIMAP5<\/jats:italic> has been associated with autoimmune diseases although its function is poorly defined. 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