Given this strong tolerization capacity of LRH-1/NR5A2 activation in mouse models of T1D, and aiming for its clinical applicability, herein we sought to determine whether LRH-1/NR5A2 activation could facilitate long-term human islet engraftment and function in immunocompetent hyperglycemic mice. The gene discussed is NR5A2; the disease is type 1 diabetes mellitus.