The tumor protein D52-like 3 (TPD52L3) gene plays a key role in the development of type 2 diabetes mellitus, and this study further investigates the contribution of lipid droplets, amphipathic helices, and protein TPD52L3 to the onset of type 2 diabetes mellitus. Besides significant understanding in the molecular background of the onset and progress of type 2 diabetes mellitus, a remarkable outcome is that it examines the possibility of prescribing synthetic human protein TPD52L3 in type 2 diabetes mellitus to overcome the reduction in the functional lipid droplets (LDs), which exists due to the downregulation of the TPD52L3 gene.