Tissue transglutaminase is a multifunctional enzyme, exerting intra and extracellular, enzymatic and nonenzymatic, Ca2+ dependent and independent functions. Its specific autoantibody, the anti transglutaminase2 autoantibody is multifunctional, affecting many of the enzyme activities. Most of them are due to loss of function, the minority being gain of function of the enzyme. No beneficial protective effects, but only pathogenic ones, were assigned to those celiac disease associated anti TG2 autoantibodies. Taken together, celiac antibodies could collectively promote small bowel intestinal or extraintestinal damage. Yet, most of the transglutaminase2 autoantibody activities where explored in vitro and ex-vivo, very few in animal model but none in vivo, in human. The celiac disease serum contains numerous antibodies, IgA-transglutaminase2 is only one of them and up till now, its differential role in celiac disease induction and maintenance is far from being unraveled. Unraveling them might open some new therapeutic strategies for celiac disease.