TRPML1 | Transient Receptor Potential Cation Channel Subfamily ML Member 1

Transient  receptor potential channels


Most TRP channels are composed of 6 transmembrane domains (helices) with intracellular N- and C-termini, non-selectively permeable to various cations

TRPML1 (Mucolipin-1): Background information

Mucolipin-1, also called TRPML1 (transient receptor potential cation channel, mucolipin subfamily, member 1) is a lysosomal cation/Ca2+ channel: It is proposed to play a major role in Ca2+ release from late endosome and lysosome vesicles to the cytoplasm, which is important for many lysosome-dependent cellular events, including the fusion and trafficking of these organelles, exocytosis and autophagy. The channel is constitutively active and the current potentiated by extracellular acidification (equivalent to intralysosomal acidification).


Human Protein:
UniProt Q8IZK6

The transmembrane protein localizes to intracellular vesicular membranes including lysosomes, it is widely expressed in adult and fetal tissues, highest expression level in adrenal gland

Function/ Application:
TRPML1 functions in the late endocytic pathway and in the regulation of lysosomal exocytosis. The channel is permeable to Ca2+, Na+, K+, and H+, as well as diverse metal ions as Fe2+, Zn2+, Ni2+, and is modulated by changes in Ca2+ concentration. TRPML1 is believed to channel iron ions across the endosome/lysosome membrane into the cell and so its malfunction causes cellular iron deficiency. TRPML1 is probably involved in Zn2+ uptake into lysosomes and required for efficient uptake of large particles in macrophages in which Ca2+ release from the lysosomes triggers lysosomal exocytosis. The channel seems to act as lysosomal active oxygen species (ROS) sensor involved in ROS-induced TFEB activation and autophagy

Mucolipidosis type IV, Niemann-Pick disease , leukomalacia, yunis-varon syndrome, cerebral palsy, ataxic, autosomal recessive

Accessory subunits:
Can heterooligomerize with MCOLN2 (TRPML2) or MCOLN3 (TRPML3)


In lysosomes activated by PtdIns(3,5)P2 (Phosphatidylinositol 3,5-bisphosphate) and at the plasma membrane inhibited by PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate). activators: ML SA1, MK6-83, SF-22, SF-51, blocker: La3+,

Patch Clamp: whole lysosome recording

Recommended Reviews:
International Union of Pharmacology. XLIII. Compendium of voltage-gated ion channels: transient receptor potential channels., Pharmacol Rev 55(4):591-6 Clapham, et al. 2003


2015 - The backstage pass to study your favorite TRP channel

icon pap   Port-a-Patch and   icon pl   Patchliner and  icon sp96   SyncroPatch 384PE  (a predecessor model of the SyncroPatch 384) poster, TRP Meeting 2015   logo pdf   (2.2 MB)


2021 - Abnormal podocyte TRPML1 channel activity and exosome release in mice with podocyte-specific Asah1 gene deletion

icon pap Port-a-Patch publication in BBA - Molecular and Cell Biology of Lipids (2021)

Li G., Huang D., Bhat O.M., Poklis J.L., Zhang A., Zou Y., Kidd J., Gehr T.W.B., Li P-L.

2020 - Arterial Medial Calcification through Enhanced small Extracellular Vesicle Release in Smooth Muscle-Specific Asah1 Gene Knockout Mice

icon pap  Port-a-Patch publication in Nature Scientific Reports (2020)

Bhat O.M., Li G., Yuan X., Huang D., Gulbins E., Kukreja R.C., Li P-L.

2019 - Purification of Functional Human TRP Channels Recombinantly Produced in Yeast

Icon Orbit Mini   Orbit mini publication in Cells (2019)

Zhang L., Wang K., Klaerke D.A., Calloe K., Lowrey L., Pedersen P.A., Gourdon P., Gotfryd K.

2019 - Control of Lysosomal TRPML1 Channel Activity and Exosome Release by Acid Ceramidase in Mouse Podocytes

icon pap   Port-a Patch Publication in American Journal of Physiology Cell Physiology (2019)

Li G., Huang D., Hong J., Bhat O.M., Yuan X., Li P.L.

2014 - A small molecule restores function to TRPML1 mutant isoforms responsible for mucolipidosis type IV

icon pap  Port-a-Patch publication in Nature Communications (2014)

Chen C.C., Keller M., Hess M., Schiffmann R., Urban N., Wolfgardt A., Schaefer M., Bracher F., Biel M., Wahl-Schott C., Grimm C.

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