In conclusion, our study identified that EVs/exosomes are key regulators of cyst formation in ADPKD and support a “cystic EVs/exosomes theory”, in that EVs/exosomes derived from cystic renal epithelia cells could affect the biology of neighboring cells, including Pkd1 heterozygous renal epithelial cells, fibroblasts, and microphages. Here, PKD1 is linked to cyst.