Reversible ubiquitylation is involved in regulating diverse cellular processes, including many germane to cancer.20, 21, 22, 23, 24 Several components of the PI3K pathway are ubiquitylated, including PTEN, which is both monoubiquitylated and polyubiquitylated, leading to nuclear localization and proteasomal degradation, respectively.25, 26, 27 The DUB USP7 can reverse PTEN monoubiquitylation, affecting its cellular localization;28 however, to date no DUBs have been described that reverse PTEN polyubiquitylation or otherwise influence PTEN expression levels. Here, PTEN is linked to cancer.