It has been reported in previous studies that NEDD4-1 and WWP2 are the only two well-defined proto-oncogenic ubiquitin ligases for PTEN degradation; however, PTEN is a stable protein with a long half-life, and only a very robust overexpression of NEDD4-1 can lead to the downregulation of PTEN protein levels in cancer cells [20–22]. The gene discussed is NEDD4; the disease is cancer.