Autoimmune diseases are characterized by multiple autoantibodies and/or autoreactive T cells that recognize a large number of antigens. Many of these antigens undergo extensive post-translational modifications during apoptosis and act as substrates for the proapoptotic cystein proteases. Here, Mauro Piacentini and Vittorio Colizzi discuss the effects on autoimmunity produced by post-translational modifications of proteins catalysed by the proapoptotic enzyme tissue transglutaminase.