On the PHLPPside: Emerging roles of PHLPP phosphatases in the heart

Cell Signal. 2021 Oct:86:110097. doi: 10.1016/j.cellsig.2021.110097. Epub 2021 Jul 25.


PH domain leucine-rich repeat protein phosphatase (PHLPP) is a family of enzymes made up of two isoforms (PHLPP1 and PHLPP2), whose actions modulate intracellular activity via the dephosphorylation of specific serine/threonine (Ser/Thr) residues on proteins such as Akt. Recent data generated in our lab, supported by findings from others, implicates the divergent roles of PHLPP1 and PHLPP2 in maintaining cellular homeostasis since dysregulation of these enzymes has been linked to various pathological states including cardiovascular disease, diabetes, ischemia/reperfusion injury, musculoskeletal disease, and cancer. Therefore, development of therapies to modulate specific isoforms of PHLPP could prove to be therapeutically beneficial in several diseases especially those targeting the cardiovascular system. This review is intended to provide a comprehensive summary of current literature detailing the role of the PHLPP isoforms in the development and progression of heart disease.

Keywords: Akt; Cardiac hypertrophy; Cardiovascular disease; PHLPP; Phosphatase; Serine/threonine.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Humans
  • Neoplasms* / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Phosphoprotein Phosphatases* / metabolism
  • Protein Isoforms / genetics
  • Proto-Oncogene Proteins c-akt / metabolism


  • Nuclear Proteins
  • Protein Isoforms
  • Proto-Oncogene Proteins c-akt
  • PHLPP2 protein, human
  • Phosphoprotein Phosphatases