Related Experiment Video

Updated: Jan 10, 2026

Author Spotlight: Establishing a New Fluorescence-Based Protocol for In Vivo Mitochondrial Morphology Analysis in Parkinson's Disease
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Is the Parkinson's-associated protein TMEM175 a proton channel: Yay or nay?

Spencer A Freeman1,2, Sergio Grinstein1,2

  • 1Program in Cell Biology, The Hospital for Sick Children , Toronto, Canada.

The Journal of Cell Biology
|November 26, 2025
PubMed

Insights

TMEM175 was thought to cause Parkinson's disease via faulty proton (H+) leakage from lysosomes. New research shows TMEM175 is actually a potassium (K+) channel, with minimal H+ permeability, revising its role in disease.

Area of Science:

  • Cell Biology
  • Neuroscience
  • Ion Channel Physiology

Background:

  • Lysosomal dysfunction and abnormal protein degradation are key in Parkinson's disease pathogenesis.
  • The transmembrane protein 175 (TMEM175) was previously hypothesized to contribute to Parkinson's via impaired proton (H+) leakage from lysosomes.

Purpose of the Study:

  • To re-evaluate the ion transport properties of TMEM175.
  • To clarify the role of TMEM175 in lysosomal function and its potential link to Parkinson's disease.

Main Methods:

  • Electrophysiological recordings to assess TMEM175 ion permeability.
  • Biochemical assays to analyze protein function in cellular models.

Main Results:

  • TMEM175 functions primarily as a potassium (K+) channel.
  • TMEM175 exhibits minimal permeability to protons (H+).
  • This finding challenges the previous model implicating defective H+ leakage through TMEM175 in Parkinson's disease.

Conclusions:

  • The established role of TMEM175 in Parkinson's disease pathogenesis needs revision.
  • TMEM175's function as a K+ channel suggests alternative mechanisms for its involvement in lysosomal homeostasis and neurodegeneration.

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