Inherited disorders of lysosomal membrane transporters

Biochim Biophys Acta Biomembr. 2020 Dec 1;1862(12):183336. doi: 10.1016/j.bbamem.2020.183336. Epub 2020 May 8.


Disorders caused by defects in lysosomal membrane transporters form a distinct subgroup of lysosomal storage disorders (LSDs). To date, defects in only 10 lysosomal membrane transporters have been associated with inherited disorders. The clinical presentations of these diseases resemble the phenotypes of other LSDs; they are heterogeneous and often present in children with neurodegenerative manifestations. However, for pathomechanistic and therapeutic studies, lysosomal membrane transport defects should be distinguished from LSDs caused by defective hydrolytic enzymes. The involved proteins differ in function, localization, and lysosomal targeting, and the diseases themselves differ in their stored material and therapeutic approaches. We provide an overview of the small group of disorders of lysosomal membrane transporters, emphasizing discovery, pathomechanism, clinical features, diagnostic methods and therapeutic aspects. We discuss common aspects of lysosomal membrane transporter defects that can provide the basis for preclinical research into these disorders.

Keywords: Lysosomal ion transport; Lysosomal metabolite export; Lysosomal metabolite import; Lysosomal storage disease (LSD); Lysosomal targeting motif; Organelle acidification; Solute carrier transporter (SLC).

Publication types

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

MeSH terms

  • Amino Acid Transport Systems, Neutral / genetics
  • Amino Acid Transport Systems, Neutral / metabolism
  • Cystinosis / genetics
  • Cystinosis / pathology
  • Histiocytosis / genetics
  • Histiocytosis / pathology
  • Humans
  • Lysosomal Storage Diseases / genetics
  • Lysosomal Storage Diseases / pathology*
  • Lysosomes / metabolism*
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism*
  • Nucleoside Transport Proteins / genetics
  • Nucleoside Transport Proteins / metabolism
  • Organic Anion Transporters / genetics
  • Organic Anion Transporters / metabolism
  • Sialic Acid Storage Disease / genetics
  • Sialic Acid Storage Disease / pathology
  • Symporters / genetics
  • Symporters / metabolism


  • Amino Acid Transport Systems, Neutral
  • CTNS protein, human
  • Membrane Transport Proteins
  • Nucleoside Transport Proteins
  • Organic Anion Transporters
  • SLC29A3 protein, human
  • Symporters
  • sialic acid transport proteins

Supplementary concepts

  • Free sialic acid storage disease