The molecular basis of mucolipidosis type IV

Curr Mol Med. 2002 Aug;2(5):445-50. doi: 10.2174/1566524023362276.


Mucolipidosis Type IV (MLIV) is a lysosomal storage disorder that is characterized by severe neurologic and ophthalmologic abnormalities. It is a progressive disease that usually presents during the first year of life with mental retardation, corneal opacities, and delayed motor milestones. First described in 1974, MLIV is a rare autosomal recessive disease and the majority of patients diagnosed to date are of Ashkenazi Jewish descent. MLIV was originally classified as a lysosomal storage disorder due to the abnormal accumulation of mucopolysaccharides and lipids. Extensive studies in MLIV cells, however, have shown that the abnormal storage is due to a defect in the late endocytic pathway. Positional cloning led to the recent discovery of a novel gene on human chromosome 19, MCOLN1, that is mutated in MLIV. To date 14 independent mutations have been reported in MCOLN1, with two mutations accounting for 95% of the Ashkenazi Jewish MLIV alleles. The identification of the MLIV gene has led to a simple tool for definitive diagnosis and will permit carrier screening in the Ashkenazi Jewish population. MCOLN1 is a new member of the transient receptor potential (TRP) cation channel gene family. The protein encoded by MCOLN1, mucolipin-1, has six predicted transmembrane domains and a putative channel pore. The identification of mutations in MCOLN1 represents the first example of a neurological disease caused by a TRP-related channel. While the function of mucolipin-1 is currently unknown, homology to the TRP superfamily and the recent description of the C. elegans mucolipin-1 homolog allow us to begin to speculate about the role of mucolipin-1 in diverse cellular processes.

Publication types

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

MeSH terms

  • Chromosomes, Human, Pair 19
  • Cloning, Molecular
  • Humans
  • Membrane Proteins / genetics*
  • Models, Genetic
  • Mucolipidoses / diagnosis
  • Mucolipidoses / genetics*
  • Mucolipidoses / pathology*
  • Mutation
  • RNA, Messenger / metabolism
  • TRPM Cation Channels
  • Transient Receptor Potential Channels


  • MCOLN1 protein, human
  • Membrane Proteins
  • RNA, Messenger
  • TRPM Cation Channels
  • Transient Receptor Potential Channels