Specifically, they suggest that PIP5Kα increases the plasma membrane PI(4,5)P2 level and contributes to breast cancer cell proliferation through PI3K/Akt activation, while the whole process can be negatively controlled by the ubiquitin ligase NEDD4, which can interact with the C-terminal region and ubiquitinate PIP5Kα (49). This evidence concerns the gene AKT1 and breast cancer.