Consistent with this view, murine studies in which the podocyte-specific ablation of Tsc1 led to “super-activation” of mTORC1 show that excessive signaling alone is sufficient to provoke FSGS, whereas more modest, physiologic levels of mTORC1 activity do not cause disease, unless an additional stressor is present.45 Here, TSC1 is linked to focal segmental glomerulosclerosis.