Handb Exp Pharmacol. 2014:222:659-74. doi: 10.1007/978-3-642-54215-2_26.


TRPML3 belongs to the MCOLN (TRPML) subfamily of transient receptor potential (TRP) channels comprising three genes in mammals. Since the discovery of the pain sensing, capsaicin- and heat-activated vanilloid receptor (TRPV1), TRP channels have been found to be involved in regulating almost all kinds of our sensory modalities. Thus, TRP channel members are sensitive to heat or cold; they are involved in pain or osmosensation, vision, hearing, or taste sensation. Loss or mutation of TRPML1 can cause retina degeneration and eventually blindness in mice and men (mucolipidosis type IV). Gain-of-function mutations in TRPML3 cause deafness and circling behavior in mice. A special feature of TRPML channels is their intracellular expression. They mostly reside in membranes of organelles of the endolysosomal system such as early and late endosomes, recycling endosomes, lysosomes, or lysosome-related organelles. Although the physiological roles of TRPML channels within the endolysosomal system are far from being fully understood, it is speculated that they are involved in the regulation of endolysosomal pH, fusion/fission processes, trafficking, autophagy, and/or (hormone) secretion and exocytosis.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Membrane Permeability
  • Gene Expression Regulation
  • Genetic Predisposition to Disease
  • Humans
  • Ion Channel Gating
  • Membrane Potentials
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • Phenotype
  • Protein Conformation
  • Signal Transduction
  • Structure-Activity Relationship
  • Transient Receptor Potential Channels / chemistry
  • Transient Receptor Potential Channels / deficiency
  • Transient Receptor Potential Channels / genetics
  • Transient Receptor Potential Channels / metabolism*


  • MCOLN3 protein, human
  • Mcoln3 protein, mouse
  • Transient Receptor Potential Channels