Genetic diseases of the Kennedy pathways for membrane synthesis

J Biol Chem. 2020 Dec 18;295(51):17877-17886. doi: 10.1074/jbc.REV120.013529.


The two branches of the Kennedy pathways (CDP-choline and CDP-ethanolamine) are the predominant pathways responsible for the synthesis of the most abundant phospholipids, phosphatidylcholine and phosphatidylethanolamine, respectively, in mammalian membranes. Recently, hereditary diseases associated with single gene mutations in the Kennedy pathways have been identified. Interestingly, genetic diseases within the same pathway vary greatly, ranging from muscular dystrophy to spastic paraplegia to a childhood blinding disorder to bone deformations. Indeed, different point mutations in the same gene (PCYT1; CCTα) result in at least three distinct diseases. In this review, we will summarize and review the genetic diseases associated with mutations in genes of the Kennedy pathway for phospholipid synthesis. These single-gene disorders provide insight, indeed direct genotype-phenotype relationships, into the biological functions of specific enzymes of the Kennedy pathway. We discuss potential mechanisms of how mutations within the same pathway can cause disparate disease.

Keywords: genetic disease; inherited; lipid; membrane; metabolism; phosphatidylcholine; phosphatidylethanolamine; phospholipid.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Choline Kinase / chemistry
  • Choline Kinase / genetics
  • Choline-Phosphate Cytidylyltransferase / chemistry
  • Choline-Phosphate Cytidylyltransferase / genetics
  • Cytidine Diphosphate / analogs & derivatives*
  • Cytidine Diphosphate / metabolism
  • Cytidine Diphosphate Choline / metabolism*
  • Ethanolamines / metabolism*
  • Genetic Association Studies
  • Humans
  • Muscular Dystrophies / congenital
  • Muscular Dystrophies / genetics
  • Muscular Dystrophies / pathology
  • Osteochondrodysplasias / congenital
  • Osteochondrodysplasias / genetics
  • Osteochondrodysplasias / pathology
  • Polymorphism, Single Nucleotide


  • Ethanolamines
  • CDP ethanolamine
  • Cytidine Diphosphate Choline
  • Cytidine Diphosphate
  • CHKB protein, human
  • Choline Kinase
  • Choline-Phosphate Cytidylyltransferase
  • PCYT1A protein, human

Supplementary concepts

  • Strudwick syndrome

Grant support