INS and type 2 diabetes mellitus: These include: (i) establishment of PITPNA as a major regulator of PtdIns-4-P signaling in the TGN of human pancreatic beta-cells, (ii) demonstration that PITPNA is required for efficient insulin granule maturation, docking, secretion, and proinsulin processing in mammalian (including human) pancreatic beta-cells, and (iii) demonstration that restoration of PITPNA expression in human T2D beta-cells rescues insulin secretion, granule maturation and alleviates ER stress.