In turn, the PH domain leucine-rich repeat protein phosphatases (PHLPP1 and PHLPP2) dephosphorylate AKT on its hydrophobic motif (Ser473 in humans) (294), whereby the loss of PHLPP activity, which appears to frequently occur in cancer, results in AKT hyperphosphorylation (295). The gene discussed is AKT1; the disease is cancer.