The significance of Ras activation, which peaks shortly after cup closure (Welliver and Swanson, 2012; Egami et al., 2014), as well as of the antagonistic behavior of PI3Ks and PTEN in the initiation and termination of cup formation is nicely documented by the observations that injection of Ras in cells induces ruffle formation, that inhibitors of PI3K inhibit cup closure in macrophages, and that deletion of PTEN in prostate cancer cells enhances macropinocytosis (Bohdanowicz and Grinstein, 2013; Levin et al., 2015; Kim et al., 2018; King and Kay, 2019). This evidence concerns the gene PTEN and Familial prostate cancer.