text: PHLPP is a member of the PPM family of phosphatases, which requires magnesium or manganese for their activity and are insensitive to most common phosphatase inhibitors, including [okadaic acid].  PHLPP1 and PHLPP2 have a similar domain structure, which includes a putative Ras association domain, a pleckstrin homology domain, a series of leucine-rich repeats, a PP2C phosphatase domain, and a C-terminal PDZ ligand.  PHLPP1 has two splice variants, PHLPP1α and PHLPP1β, of which PHLPP1β is larger by approximately 1.5 kilobase pairs.  PHLPP1α, which was the first PHLPP isoform to be characterized, lacks the N-terminal portion of the protein, including the Ras association domain.   PHLPP's domain structure influences its ability to dephosphorylate its substrates.  A PHLPP construct lacking the PH domain is unable to decrease PKC phosphorylation, while PHLPP lacking the PDZ ligand is unable to decrease Akt phosphorylation.