mTORC1 signaling is normally activated by nutrients such as amino acids and growth factors. The primary signals for mTORC2 activation are unknown. Activation of mTORC1, as occurs in diabetic nephropathy, results in effaced foot processes and proteinuria and also is associated with mesangial expansion. mTORC1 activation may also result in transition of the podocyte to a more mesenchymal phenotype, resulting in loss of adhesion to the underlying GBM and detachment, further promoting proteinuria and ultimately sclerosis. Rapamycin has an immediate inhibitory effect on mTORC1 and with chronic use may also, through unknown mechanisms, inhibit mTORC2. Inhibition of mTORC1, especially during development or other physiologic or pathophysiologic growth, may also cause podocyte injury (8, 9). Added inhibition of mTORC2 activation causes more severe podocyte injury, sclerosis, and proteinuria (8), illustrating the dependence of normal podocyte function and structure on balance of the two complexes.