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 (PubMed:20819118). Isoform 2 seems to have a major role in regulating Akt signaling in hippocampal neurons while isoform 1 may promote Akt and PKC activation and inhibit ERK signaling (PubMed:20819118). 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 (By similarity). Dephosphorylates RPS6KB1 and is involved in regulation of cap-dependent translation (By similarity). Inhibits cancer cell proliferation and may act as a tumor suppressor (By similarity). Dephosphorylates RAF1 inhibiting its kinase activity (By similarity). May act as a negative regulator of K-Ras signaling in membrane rafts (PubMed:12594205). Involved in the hippocampus-dependent long-term memory formation (By similarity). Involved in circadian control by regulating the consolidation of circadian periodicity after resetting (By similarity). Involved in development and function of regulatory T-cells (By similarity). 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 (PubMed:12594205). Interacts with AKT2, AKT3 and PRKCB isoform beta-II. Interacts with WDR48 and USP12 (By similarity). Mainly present in brain (at protein level) (PubMed:10570941). Isoform 2 is more abundant in adult brain neurons than isoform 1 in (PubMed:20819118). Isoforms 1 and 2 are expressed in the retina but not found in rod outer segments (PubMed:20089132). In the suprachiasmatic nucleus, it increases during subjective night with a peak at midnight under constant dark conditions. Expressed at a constant level in neurons throughout the brain (at protein level) (PubMed:10570941). Isoform 2 expression increases over development and maturation in the hippocampus. Isoform 1 expression is low in embryonic stages, increases during postnatal development and is falling back to low embryonic levels in adulthood (PubMed:20819118). Inhibited by insulin in a PI3K-dependent manner. The PH domain is required for interaction with PRKCB and its dephosphorylation.