<i>In vitro</i> studies examined rhMG53's effects on NLRP3 inflammasome activation, caspase-1 cleavage, interleukin-1β (IL-1β) secretion, and MG53-NLRP3 interactions.<h4>Results</h4><i>MG53</i> <sup>-/-</sup> mice showed more severe colitis with increased weight loss, higher disease activity scores, shortened colons, and greater inflammation. The gene discussed is NLRP3; the disease is colitis.