Diabetic Nephropathy (DN) is the leading cause of end stage renal disease and represents a major burden on our health care system. Key event in the initiation and progression of DN is the injury and loss of highly specialized cells called podocytes that form the outer part of the glomerular filtration unit. We have developed an exquisite experimental platform that facilitates the systematic unravelling of the signaling networks leading to (1) the initiation, (2) the progression and (3) the potential regeneration of podocytes in DN, paving the way to novel therapeutic strategies.