The expanding spectrum of neurological disorders of phosphoinositide metabolism

Jonathan R. Volpatti, Almundher Al-Maawali, Lindsay Smith, Aqeela Al-Hashim, Julie A. Brill, James J. Dowling*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)


Phosphoinositides (PIPs) are a ubiquitous group of seven low-abundance phospholipids that play a crucial role in defining localized membrane properties and that regulate myriad cellular processes, including cytoskeletal remodeling, cell signaling cascades, ion channel activity and membrane traffic. PIP homeostasis is tightly regulated by numerous inositol kinases and phosphatases, which phosphorylate and dephosphorylate distinct PIP species. The importance of these phospholipids, and of the enzymes that regulate them, is increasingly being recognized, with the identification of human neurological disorders that are caused by mutations in PIP-modulating enzymes. Genetic disorders of PIP metabolism include forms of epilepsy, neurodegenerative disease, brain malformation syndromes, peripheral neuropathy and congenital myopathy. In this Review, we provide an overview of PIP function and regulation, delineate the disorders associated with mutations in genes that modulate or utilize PIPs, and discuss what is understood about gene function and disease pathogenesis as established through animal models of these diseases.

Original languageEnglish
Article numberdmm038174
JournalDMM Disease Models and Mechanisms
Issue number8
Publication statusPublished - 2019


  • ALS
  • Charcot Marie Tooth disease
  • Congenital myopathy
  • Neurogenetic
  • Phosphoinositides

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Medicine (miscellaneous)
  • Immunology and Microbiology (miscellaneous)
  • General Biochemistry,Genetics and Molecular Biology


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