Lipins, lipinopathies, and the modulation of cellular lipid storage and signaling

Prog Lipid Res. 2013 Jul;52(3):305-16. doi: 10.1016/j.plipres.2013.04.001. Epub 2013 Apr 17.


Members of the lipin protein family are phosphatidate phosphatase (PAP) enzymes, which catalyze the dephosphorylation of phosphatidic acid to diacylglycerol, the penultimate step in TAG synthesis. Lipins are unique among the glycerolipid biosynthetic enzymes in that they also promote fatty acid oxidation through their activity as co-regulators of gene expression by DNA-bound transcription factors. Lipin function has been evolutionarily conserved from a single ortholog in yeast to the mammalian family of three lipin proteins-lipin-1, lipin-2, and lipin-3. In mice and humans, the levels of lipin activity are a determinant of TAG storage in diverse cell types, and humans with deficiency in lipin-1 or lipin-2 have severe metabolic diseases. Recent work has highlighted the complex physiological interactions between members of the lipin protein family, which exhibit both overlapping and unique functions in specific tissues. The analysis of "lipinopathies" in mouse models and in humans has revealed an important role for lipin activity in the regulation of lipid intermediates (phosphatidate and diacylglycerol), which influence fundamental cellular processes including adipocyte and nerve cell differentiation, adipocyte lipolysis, and hepatic insulin signaling. The elucidation of lipin molecular and physiological functions could lead to novel approaches to modulate cellular lipid storage and metabolic disease.

Publication types

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

MeSH terms

  • Animals
  • Diglycerides / metabolism
  • Humans
  • Organic Chemicals / metabolism
  • Phosphatidate Phosphatase / chemistry
  • Phosphatidate Phosphatase / genetics
  • Phosphatidate Phosphatase / metabolism*
  • Phosphatidic Acids / metabolism
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Rhabdomyolysis / metabolism
  • Rhabdomyolysis / pathology
  • Signal Transduction
  • Triglycerides / metabolism*


  • Diglycerides
  • Organic Chemicals
  • Phosphatidic Acids
  • Protein Isoforms
  • Triglycerides
  • lipine
  • Phosphatidate Phosphatase