Protein phosphatase involved in regulation of Akt and PKC signaling. Mediates dephosphorylation in the C-terminal domain hydrophobic motif of members of the AGC Ser/Thr protein kinase family; specifically acts on 'Ser-473' of AKT2 and AKT3, 'Ser-660' of PRKCB and 'Ser-657' of PRKCA (By similarity). Isoform 2 seems to have a major role in regulating Akt signaling in hippocampal neurons (By similarity). Akt regulates the balance between cell survival and apoptosis through a cascade that primarily alters the function of transcription factors that regulate pro- and antiapoptotic genes. Dephosphorylation of 'Ser-473' of Akt triggers apoptosis and suppression of tumor growth. Dephosphorylation of PRKCA and PRKCB leads to their destabilization and degradation. Dephosphorylates STK4 on 'Thr-387' leading to STK4 activation and apoptosis. Dephosphorylates RPS6KB1 and is involved in regulation of cap-dependent translation. Inhibits cancer cell proliferation and may act as a tumor suppressor. Dephosphorylates RAF1 inhibiting its kinase activity. May act as a negative regulator of K-Ras signaling in membrane rafts (By similarity). Involved in the hippocampus-dependent long-term memory formation (PubMed:17382888). Involved in circadian control by regulating the consolidation of circadian periodicity after resetting (PubMed:20080691). Involved in development and function of regulatory T-cells (PubMed:21498666). H2O + O-phospho-L-seryl-[protein] = L-seryl-[protein] + phosphate H2O + O-phospho-L-threonyl-[protein] = L-threonyl-[protein] + phosphate Binds 2 manganese ions per subunit. Insensitive to okadaic acid. Deubiquitination by WDR48-USP12 complex positively regulates PHLPP1 stability. Interacts with the nucleotide free form of K-Ras (KRAS) via its LRR repeats (By similarity). Interacts with AKT2, AKT3 and PRKCB. Interacts with WDR48 and USP12 (By similarity). Isoforms 1 and 2 are expressed in the retina (PubMed:20089132). Up-regulated in the hippocampus upon chronic methamphetamine treatment. The PH domain is required for interaction with PRKCB and its dephosphorylation.