Together, our in vivo and in vitro studies identified multiple roles for Hpse in T1D, namely promoting the migration of leukocytes from pancreatic blood vessels (i.e., across the sub-endothelial BM and through the pancreatic ECM), aiding the passage of leukocytes across the islet BM and depleting islet beta cells of the intracellular HS needed for their survival (Figure 2). This evidence concerns the gene HPSE and type 1 diabetes mellitus.