Gene Symbol: TRPML1
Description: mucolipin 1
Alias: 2210015I05Rik, TRPML1, mucolipidin, mucolipin-1, transient receptor potential-mucolipin 1
Species: mouse
Products:     TRPML1

Top Publications

  1. Micsenyi M, Dobrenis K, Stephney G, Pickel J, Vanier M, Slaugenhaupt S, et al. Neuropathology of the Mcoln1(-/-) knockout mouse model of mucolipidosis type IV. J Neuropathol Exp Neurol. 2009;68:125-35 pubmed publisher
    The recently developed Mcoln1(-/-) knockout mouse provides a novel model for analyzing mucolipin 1 function and mucolipidosis type IV disease. Here we characterize the neuropathology of Mcoln1(-/-) mouse at the end stage...
  2. Venkatachalam K, Hofmann T, Montell C. Lysosomal localization of TRPML3 depends on TRPML2 and the mucolipidosis-associated protein TRPML1. J Biol Chem. 2006;281:17517-27 pubmed
    ..The disease arises due to mutations in a group 2 transient receptor potential (TRP)-related cation channel, TRPML1. Mammals encode two additional TRPML proteins named TRPML2 and TRPML3...
  3. Thompson E, Schaheen L, Dang H, Fares H. Lysosomal trafficking functions of mucolipin-1 in murine macrophages. BMC Cell Biol. 2007;8:54 pubmed
    ..Mucolipin-1 functions in the efficient exit of molecules, destined for various cellular organelles, from lysosomal compartments. ..
  4. Venugopal B, Browning M, Curcio Morelli C, Varro A, Michaud N, Nanthakumar N, et al. Neurologic, gastric, and opthalmologic pathologies in a murine model of mucolipidosis type IV. Am J Hum Genet. 2007;81:1070-83 pubmed
    ..In addition, this model provides an invaluable resource for testing treatment strategies and potential therapies aimed at preventing or ameliorating the abnormal lysosomal storage in this devastating neurological disorder...
  5. Samie M, Grimm C, Evans J, Curcio Morelli C, Heller S, Slaugenhaupt S, et al. The tissue-specific expression of TRPML2 (MCOLN-2) gene is influenced by the presence of TRPML1. Pflugers Arch. 2009;459:79-91 pubmed publisher
    Mucolipidosis type IV is a lysosomal storage disorder caused by the loss or dysfunction of the mucolipin-1 (TRPML1) protein. It has been suggested that TRPML2 could genetically compensate (i.e., become upregulated) for the loss of TRPML1...
  6. Wang X, Zhang X, Dong X, Samie M, Li X, Cheng X, et al. TPC proteins are phosphoinositide- activated sodium-selective ion channels in endosomes and lysosomes. Cell. 2012;151:372-83 pubmed publisher
    ..These findings suggest that the organellar membrane potential may undergo large regulatory changes and may explain the specificity of PI(3,5)P(2) in regulating the fusogenic potential of intracellular organelles. ..
  7. Eichelsdoerfer J, Evans J, Slaugenhaupt S, Cuajungco M. Zinc dyshomeostasis is linked with the loss of mucolipidosis IV-associated TRPML1 ion channel. J Biol Chem. 2010;285:34304-8 pubmed publisher
    ..MLIV is caused by the loss of TRPML1 ion channel function...
  8. Xu H, Delling M, Li L, Dong X, Clapham D. Activating mutation in a mucolipin transient receptor potential channel leads to melanocyte loss in varitint-waddler mice. Proc Natl Acad Sci U S A. 2007;104:18321-6 pubmed
    ..Mutations in human TRPML1 (mucolipin 1/MCOLN1) result in mucolipidosis type IV, a severe inherited neurodegenerative disease associated with defective ..
  9. Dong X, Cheng X, Mills E, Delling M, Wang F, Kurz T, et al. The type IV mucolipidosis-associated protein TRPML1 is an endolysosomal iron release channel. Nature. 2008;455:992-6 pubmed publisher
    TRPML1 (mucolipin 1, also known as MCOLN1) is predicted to be an intracellular late endosomal and lysosomal ion channel protein that belongs to the mucolipin subfamily of transient receptor potential (TRP) proteins...

More Information


  1. Li X, Rydzewski N, Hider A, Zhang X, Yang J, Wang W, et al. A molecular mechanism to regulate lysosome motility for lysosome positioning and tubulation. Nat Cell Biol. 2016;18:404-17 pubmed publisher
    ..Mutations of the lysosomal Ca(2+) channel TRPML1 cause lysosomal storage disease (LSD) characterized by disordered lysosomal membrane trafficking in cells...
  2. Xu M, Li X, Walsh S, Zhang Y, Abais J, Boini K, et al. Intracellular two-phase Ca2+ release and apoptosis controlled by TRP-ML1 channel activity in coronary arterial myocytes. Am J Physiol Cell Physiol. 2013;304:C458-66 pubmed publisher
    ..arterial myocytes (CAMs), which consists of local Ca(2+) bursts via lysosomal transient potential receptor-mucolipin 1 (TRP-ML1) channels and consequent Ca(2+) release from the sarcoplasmic reticulum (SR)...
  3. Zhang X, Li X, Xu H. Phosphoinositide isoforms determine compartment-specific ion channel activity. Proc Natl Acad Sci U S A. 2012;109:11384-9 pubmed publisher
    ..localized channels are similarly "inactivated" at the PM, we studied PIP(2) modulation of intracellular TRPML1 channels...
  4. Zhang S, Li N, Zeng W, Gao N, Yang M. Cryo-EM structures of the mammalian endo-lysosomal TRPML1 channel elucidate the combined regulation mechanism. Protein Cell. 2017;8:834-847 pubmed publisher
    b>TRPML1 channel is a non-selective group-2 transient receptor potential (TRP) channel with Ca2+ permeability...
  5. Grishchuk Y, Stember K, Matsunaga A, Olivares A, CRUZ N, King V, et al. Retinal Dystrophy and Optic Nerve Pathology in the Mouse Model of Mucolipidosis IV. Am J Pathol. 2016;186:199-209 pubmed publisher
    ..Our data suggest that mucolipin-1 plays a role in postnatal development of photoreceptors and provides a set of outcome measures that can be used for ocular therapy development for mucolipidosis IV. ..
  6. Li X, Saitoh S, Shibata T, Tanimura N, Fukui R, Miyake K. Mucolipin 1 positively regulates TLR7 responses in dendritic cells by facilitating RNA transportation to lysosomes. Int Immunol. 2015;27:83-94 pubmed publisher
    ..We here show that Mucolipin 1 (Mcoln1), a member of the transient receptor potential (TRP) cation channel gene family, has an important role ..
  7. Park S, Ahuja M, Kim M, Brailoiu G, Jha A, Zeng M, et al. Fusion of lysosomes with secretory organelles leads to uncontrolled exocytosis in the lysosomal storage disease mucolipidosis type IV. EMBO Rep. 2016;17:266-78 pubmed publisher
    Mutations in TRPML1 cause the lysosomal storage disease mucolipidosis type IV (MLIV). The role of TRPML1 in cell function and how the mutations cause the disease are not well understood...
  8. Chen Q, She J, Zeng W, Guo J, Xu H, Bai X, et al. Structure of mammalian endolysosomal TRPML1 channel in nanodiscs. Nature. 2017;550:415-418 pubmed publisher
    b>Transient receptor potential mucolipin 1 (TRPML1) is a cation channel located within endosomal and lysosomal membranes...
  9. REMIS N, Wiwatpanit T, Castiglioni A, Flores E, Cantú J, García Añoveros J. Mucolipin co-deficiency causes accelerated endolysosomal vacuolation of enterocytes and failure-to-thrive from birth to weaning. PLoS Genet. 2014;10:e1004833 pubmed publisher
    ..weaning express high levels of two endolysosomal cation channels, mucolipins 3 and 1 -products of Trpml3 and Trpml1 genes; moreover neonatal enterocytes of mice lacking both mucolipins (Trpml3-/-;Trpml1-/-) vacuolated ..
  10. Zhang L, Fang Y, Cheng X, Lian Y, Xu H, Zeng Z, et al. TRPML1 Participates in the Progression of Alzheimer's Disease by Regulating the PPAR?/AMPK/Mtor Signalling Pathway. Cell Physiol Biochem. 2017;43:2446-2456 pubmed publisher
    b>TRPML1 is reported to be involved in the pathogenesis of Alzheimer's disease (AD) by regulating autophagy; however, the underlying mechanism is not completely clear. We developed an APP/PS1 transgenic animal model that presents with AD...
  11. Grishchuk Y, Peña K, Coblentz J, King V, Humphrey D, Wang S, et al. Impaired myelination and reduced brain ferric iron in the mouse model of mucolipidosis IV. Dis Model Mech. 2015;8:1591-601 pubmed publisher mutations in the MCOLN1 gene, which encodes the lysosomal transient receptor potential ion channel mucolipin-1 (TRPML1). MLIV causes impaired motor and cognitive development, progressive loss of vision and gastric achlorhydria...
  12. Miller A, Schafer J, Upchurch C, Spooner E, Huynh J, Hernández S, et al. Mucolipidosis type IV protein TRPML1-dependent lysosome formation. Traffic. 2015;16:284-97 pubmed publisher
    ..In this study, we quantitatively define the multiple steps of lysosome formation and identify the first regulator of this process. ..
  13. Spooner E, McLaughlin B, Lepow T, Durns T, Randall J, Upchurch C, et al. Systematic screens for proteins that interact with the mucolipidosis type IV protein TRPML1. PLoS ONE. 2013;8:e56780 pubmed publisher the MCOLN1 gene, which encodes the endosomal/lysosomal Transient Receptor Potential channel protein mucolipin-1/TRPML1. Cells isolated from Mucolipidosis type IV patients and grown in vitro and in in vivo models of this disease both ..
  14. Dayam R, Saric A, Shilliday R, Botelho R. The Phosphoinositide-Gated Lysosomal Ca(2+) Channel, TRPML1, Is Required for Phagosome Maturation. Traffic. 2015;16:1010-26 pubmed publisher
    ..However, it is not known how PIKfyve and PtdIns(3,5)P2 participate in phagosome maturation. TRPML1 is a PtdIns(3,5)P2 -gated lysosomal Ca(2+) channel...
  15. Walker M, Montell C. Suppression of the motor deficit in a mucolipidosis type IV mouse model by bone marrow transplantation. Hum Mol Genet. 2016;25:2752-2761 pubmed
    Mucolipidosis IV (MLIV) is a severe lysosomal storage disorder, which results from loss of the TRPML1 channel. MLIV causes multiple impairments in young children, including severe motor deficits. Currently, there is no effective treatment...
  16. Takumida M, Anniko M. Expression of transient receptor potential channel mucolipin (TRPML) and polycystine (TRPP) in the mouse inner ear. Acta Otolaryngol. 2010;130:196-203 pubmed publisher
    ..To study the expression of TRPML1-3 and TRPP2, 3, and 5 in the mouse inner ear...
  17. Cheng X, Zhang X, Gao Q, Ali Samie M, Azar M, Tsang W, et al. The intracellular Ca²⁺ channel MCOLN1 is required for sarcolemma repair to prevent muscular dystrophy. Nat Med. 2014;20:1187-92 pubmed publisher
    ..MCOLN1 (also known as TRPML1, ML1) is an endosomal and lysosomal Ca(2+) channel whose human mutations cause mucolipidosis IV (ML4), a ..
  18. Jakobs H, Mikula M, Havemeyer A, Strzalkowska A, Borowa Chmielak M, Dzwonek A, et al. The N-reductive system composed of mitochondrial amidoxime reducing component (mARC), cytochrome b5 (CYB5B) and cytochrome b5 reductase (CYB5R) is regulated by fasting and high fat diet in mice. PLoS ONE. 2014;9:e105371 pubmed publisher
    ..With this study we provide further evidence that the endogenous function of the mARC protein is linked with lipid metabolism. ..
  19. Cuajungco M, Basilio L, Silva J, HART T, Tringali J, Chen C, et al. Cellular zinc levels are modulated by TRPML1-TMEM163 interaction. Traffic. 2014;15:1247-65 pubmed publisher
    Mucolipidosis type IV (MLIV) is caused by loss of function mutations in the TRPML1 ion channel...
  20. Chandra M, Zhou H, Li Q, Muallem S, Hofmann S, Soyombo A. A role for the Ca2+ channel TRPML1 in gastric acid secretion, based on analysis of knockout mice. Gastroenterology. 2011;140:857-67 pubmed publisher
    Mutations in TRPML1, a lysosomal Ca(2+)-permeable TRP channel, lead to mucolipidosis type IV, a neurodegenerative lysosomal storage disease. An unusual feature of mucolipidosis type IV is constitutive achlorhydria...
  21. Curcio Morelli C, Charles F, Micsenyi M, Cao Y, Venugopal B, Browning M, et al. Macroautophagy is defective in mucolipin-1-deficient mouse neurons. Neurobiol Dis. 2010;40:370-7 pubmed publisher
    ..This study describes, for the first time, a defect in macroautophagy in mucolipin-1-deficient neurons, which corroborates recent findings in MLIV fibroblasts and provides new insight into the neuronal pathogenesis of this disease. ..
  22. Falardeau J, Kennedy J, Acierno J, Sun M, Stahl S, Goldin E, et al. Cloning and characterization of the mouse Mcoln1 gene reveals an alternatively spliced transcript not seen in humans. BMC Genomics. 2002;3:3 pubmed
    ..While identification of Mcoln1 is crucial to the development of mouse models for MLIV, the fact that there are two transcripts in mice suggests an additional or alternate function of the gene that may complicate phenotypic assessment. ..
  23. Dong X, Wang X, Shen D, Chen S, Liu M, Wang Y, et al. Activating mutations of the TRPML1 channel revealed by proline-scanning mutagenesis. J Biol Chem. 2009;284:32040-52 pubmed publisher
    ..Mutations of human TRPML1 cause type IV mucolipidosis, a devastating pediatric neurodegenerative disease...