Su Jung Song at Soonchunhyang University, Cheonan-si, South Korea, and Min Sup Song at The University of Texas, Houston, USA, and coworkers have reviewed how DUBs can affect PTEN, reporting on the molecular mechanisms of cancer-specific DUBs, and highlighting the potential to pharmacologically target DUBs in order to boost PTEN activity and suppress cancer development. Here, PTEN is linked to cancer.