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:15808505, PubMed:17386267, PubMed:18162466). 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 (PubMed:18162466). Dephosphorylates STK4 on 'Thr-387' leading to STK4 activation and apoptosis (PubMed:20513427). Dephosphorylates RPS6KB1 and is involved in regulation of cap-dependent translation (PubMed:21986499). Inhibits cancer cell proliferation and may act as a tumor suppressor (PubMed:19079341). Dephosphorylates RAF1 inhibiting its kinase activity (PubMed:24530606). May act as a negative regulator of K-Ras signaling in membrane rafts (By similarity). 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 (By similarity). Mn(2+) is inhibitory below pH 8 and activating above pH 8 (PubMed:24892992). Insensitive to okadaic acid (PubMed:15808505). Deubiquitination by WDR48-USP12 complex positively regulates PHLPP1 stability (PubMed:24145035). Interacts with the nucleotide free form of K-Ras (KRAS) via its LRR repeats (By similarity). Interacts with AKT2, AKT3, PRKCB isoform beta-II, STK4, RPS6KB1, RAF1 (PubMed:17386267, PubMed:18162466, PubMed:19732725, PubMed:21986499, PubMed:24530606). Isoform 1 (predominantly) and isoform 2 interact with BRAP (PubMed:25820252). Interacts with FKBP5; FKBP5 acts as a scaffold for PHLPP1 and Akt (PubMed:19732725). Interacts with SCRIB; SCRIB acts as a scaffold for PHLPP1 and Akt (PubMed:21701506). Interacts with SLC9A3R1; SLC9A3R1 scaffolds a heterotrimeric complex with PTEN at the plasma membrane (PubMed:21804599). Interacts with WDR48 and USP12 (PubMed:24145035). In colorectal cancer tissue, expression is concentrated at the lateral membrane of epithelial cells. In colorectal cancer tissue, expression is highest in the surface epithelium of normal colonic mucosa adjacent to the cancer tissue but is largely excluded from the crypt bases. Expression is lost or significantly decreased in 78% of tested tumors (at protein level). Ubiquitously expressed in non-cancerous tissues. The PH domain is required for interaction with PRKCB and its dephosphorylation. Truncated N-terminus. Contaminating sequence. Potential poly-A sequence. Truncated N-terminus. Truncated N-terminus.