title: Lysosomal integral membrane protein-2: a new player in lysosome-related pathology.
abstract: Lysosomes require the presence of many specialized proteins to facilitate their roles in cellular maintenance. One such protein that has proven to be an important player in the lysosomal field is lysosomal integral membrane protein-2 (LIMP-2), encoded by the gene SCARB2. LIMP-2 is required for the normal biogenesis and maintenance of lysosomes and endosomes and has been identified as the specific receptor for glucocerebrosidase, the enzyme deficient in Gaucher disease. Research into LIMP-2 and the SCARB2 gene indicate that it may be a factor contributing to the clinical heterogeneity seen among patients with Gaucher disease. Mutations in SCARB2 have also been identified as the cause of action myoclonus renal failure (AMRF), and in some cases progressive myoclonic epilepsy. A total of 14 disease-causing SCARB2 mutations have been identified to date. The role of LIMP-2 in human pathology has expanded with its identification as a component of the intercalated disk in cardiac muscle and as a receptor for specific enteroviruses, two unanticipated findings that reaffirm the myriad roles of lysosomal proteins. Studies into the full impact of LIMP-2 deficiency and the LIMP2/glucocerebrosidase molecular pathway will lead to a better understanding of disease pathogenesis in Gaucher disease and AMRF, and to new insights into lysosomal processing, trafficking and function.
authors.affiliation: Section on Molecular Neurogenetics, Medical Genetics Branch, NHGRI, NIH, Bethesda, MD 20892, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Gonzalez
authors.affiliation: Section on Molecular Neurogenetics, Medical Genetics Branch, NHGRI, NIH, Bethesda, MD 20892, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Valeiras
authors.affiliation: Section on Molecular Neurogenetics, Medical Genetics Branch, NHGRI, NIH, Bethesda, MD 20892, USA. Electronic address: sidranse@mail.nih.gov.
authors.forename: Ellen
authors.initials: E
authors.lastname: Sidransky
authors.affiliation: Section on Molecular Neurogenetics, Medical Genetics Branch, NHGRI, NIH, Bethesda, MD 20892, USA.
authors.forename: Nahid
authors.initials: N
authors.lastname: Tayebi
mesh_terms: D000818:Animals; D005776:Gaucher Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015870:Gene Expression; D018740:Genetic Heterogeneity; D005962:Glucosylceramidase / Q000172:deficiency* / Q000235:genetics; D006801:Humans; D051907:Lysosomal Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009154:Mutation; D020191:Myoclonic Epilepsies, Progressive / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051116:Receptors, Scavenger / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D051907:Lysosomal Membrane Proteins; D051116:Receptors, Scavenger; C074299:SCARB2 protein, human; D005962:Glucosylceramidase
keywords: Action myoclonus renal failure; Gaucher disease; Glucocerebrosidase; Lysosomal integral membrane protein-2; Lysosomal membrane protein; Transporter