When EGF signaling is activated, the local concentration of PtdIns(4,5)P2 is decreased, which causes activation of PKD2, resulting in increased Ca2+ influx.85, 93 Therefore, EGF signaling can sensitize the primary cilium‐based mechanosensation by reducing the threshold of PKD2 for activation by mechanical stimulation.87 Targeted disruption of genes involved in EGF signaling, including EGFR,94, 95 PKD2,96 and USP8,26 causes cystic kidney in animal models. This evidence concerns the gene PKD2 and Renal cyst.