Recent studies found that Gα 12 activation in podocytes led to proteinuria and glomerulosclerosis via regulating collagen IV.33 Considering that β-arrestins are originally identified as negative adaptors of GPCRs and a very recent study reveals that β-arrestin-1 drives endothelin-1-mediated podocyte activation and sustains renal injury in adriamycin-induced nephropathy,34 it is very possible that β-arrestins may also regulate GPCR signaling in podocytes by regulation of their desensitization and internalization, thereby leading to podocyte injury. This evidence concerns the gene EDN1 and glomerulosclerosis.