Lipid biology of the podocyte--new perspectives offer new opportunities

Nat Rev Nephrol. 2014 Jul;10(7):379-88. doi: 10.1038/nrneph.2014.87. Epub 2014 May 27.


In the past 15 years, major advances have been made in understanding the role of lipids in podocyte biology. First, susceptibility to focal segmental glomerulosclerosis (FSGS) and glomerular disease is associated with an APOL1 sequence variant, is expressed in podocytes and encodes apolipoprotein L1, an important component of HDL. Second, acid sphingomyelinase-like phosphodiesterase 3b encoded by SMPDL3b has a role in the conversion of sphingomyelin to ceramide and its levels are reduced in renal biopsy samples from patients with recurrent FSGS. Furthermore, decreased SMPDL3b expression is associated with increased susceptibility of podocytes to injury after exposure to sera from these patients. Third, in many individuals with membranous nephropathy, autoantibodies against the phospholipase A2 (PLA2) receptor, which is expressed in podocytes, have been identified. Whether these autoantibodies affect the activity of PLA2, which liberates arachidonic acid from glycerophospholipids and modulates podocyte function, is unknown. Fourth, clinical and experimental evidence support a role for ATP-binding cassette sub-family A member 1-dependent cholesterol efflux, free fatty acids and glycerophospolipids in the pathogenesis of diabetic kidney disease. An improved understanding of lipid biology in podocytes might provide insights to develop therapeutic targets for primary and secondary glomerulopathies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ATP Binding Cassette Transporter 1 / metabolism
  • Animals
  • Apolipoprotein L1
  • Apolipoproteins / genetics
  • Autoantibodies / pharmacology
  • Cholesterol / metabolism
  • Diabetic Nephropathies / physiopathology
  • Gangliosides / metabolism
  • Glomerulosclerosis, Focal Segmental / metabolism*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Lipid Metabolism / physiology*
  • Lipoproteins, HDL / genetics
  • Membrane Microdomains / physiology
  • Phosphatidylcholine-Sterol O-Acyltransferase / genetics
  • Phosphatidylcholine-Sterol O-Acyltransferase / metabolism
  • Phospholipases A2 / immunology
  • Phospholipases A2 / physiology
  • Podocytes / metabolism*
  • Renal Insufficiency, Chronic / drug therapy
  • Signal Transduction
  • Sphingolipids / metabolism
  • Sphingomyelin Phosphodiesterase / metabolism


  • ABCA1 protein, human
  • APOL1 protein, human
  • ATP Binding Cassette Transporter 1
  • Apolipoprotein L1
  • Apolipoproteins
  • Autoantibodies
  • Gangliosides
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipoproteins, HDL
  • Sphingolipids
  • Cholesterol
  • Phosphatidylcholine-Sterol O-Acyltransferase
  • Phospholipases A2
  • SMPDL3B protein, human
  • Sphingomyelin Phosphodiesterase