Basic research has demonstrated that MR signaling can be potentiated not only by aldosterone but through other mechanisms, such as Rac1, cortisol, hyperglycemia, and oxidative stress, and that pathological MR overactivity results in diverse pathological consequences, including glomerulosclerosis, arteriolar hyalinosis, infiltration of inflammatory cells, and fibrotic changes in the tubulointerstitium as well as the perivasculature. Here, RAC1 is linked to glomerulosclerosis.