Our results revealed that the knockdown of GEF-H1 not only restored the activation of RhoA and phosphorylation of MCL2 but also reversed cyst formation, interstitial fibrosis, and inflammation in NPHP1KO mice, and inhibited EMT changes in NPHP1KD HK2 cells by downregulating the expression of α-SMA and upregulating the expression of E-cadherin. Here, RHOA is linked to cyst.