Type 1 diabetes mellitus (T1DM) is an autoimmune disease, due to the immune-mediated destruction of pancreatic -cells,
whose incidence has been steadily increasing during the last decades. Insulin replacement therapy can treat T1DM, which, however, is
still associated with substantial morbidity and mortality. For this reason, great effort is being put into developing strategies that could
eventually prevent and/or cure this disease. These strategies are mainly focused on blocking the immune system from attacking -cells
together with functional islet restoration either by regeneration or transplantation. Recent experimental evidences suggest that TNFrelated
apoptosis-inducing ligand (TRAIL), which is an immune system modulator protein, could represent an interesting candidate for
the cure for T1DM and/or its complications. Here we review the evidences on the potential role of TRAIL in the management of T1DM.