Ion Channel Studies

TMEM175

Advance your TMEM175 drug discovery programs with our validated assay platform. Sygnature Discovery offers  wild-type and disease-relevant variant TMEM175 models, supporting high-throughput screening, detailed electrophysiology and pharmacological profiling to accelerate therapeutic innovation. 

TMEM175 as a Target for Drug Discovery

TMEM175 is a constitutively active lysosomal potassium channel, playing a key role in lysosomal pH regulations, membrane potential and autophagy. Dysfunctional TMEM175 activity has been linked to α-synuclein aggregation and impaired protein clearance- important factors in Parkinson’s disease.

Both loss-of-function (LoF) and gain-of-function (GoF) coding variants are associated with disease risk, highlighting TMEM175 as a promising but underexplored target in ion channel drug discovery.

At Sygnature Discovery, our TMEM175 platform supports the discovery of new therapeutic strategies aimed at restoring lysosomal homeostasis and addressing neurodegenerative diseases.

Access the TMEM175 Assays You Need

Sygnature Discovery offers a suite of proprietary cell lines expressing TMEM175, supporting both wild-type and variant forms as well as key species orthologs.

Our validated cell models and robust electrophysiology platforms are designed to help you:

  • Accelerate hit identification and lead optimization
  • Explore functional effects of disease-relevant TMEM175 variants 
  • Confidently advance TMEM175-targeting drug discovery programs

Need something specific? Our experience cell line generation team is also on hand to develop and validate additional TMEM175 variants to support your research.

Off-the-Shelf TMEM175 Assays 
TMEM175 (human) TMEM175 (LoF) TMEM175 (GoF)
TMEM175 (mouse) TMEM175 (rat) TMEM175 (dog) 
TMEM175 (monkey)    

Investigate TMEM175 Biology in Depth

Our TMEM175 platform allows researchers to:

  • Assess differential activation in response to extracellular acidification
  • Evaluate variant-specific pharmacological responses
  • Measure compound efficacy across disease-relevant genetic backgrounds

With side-by-side comparisons of wild-type, LoF and GoF TMEM175 variants, you can better understand how genetic diversity impacts TMEM175 activity – and discover new ways to target it.

Contact Syganture Discovery

To learn more about our services or to request a quote.

TMEM175 screening assays

High-Throughput Screening

Validated high-throughput screening assay

Electrophysiology Studies

Robust electrophysiology assays ready to run 

Cell Line Generation - SB Drug Discovery

Disease-relevant variant cell lines & assays 

Range of species orthologs

Range of species orthologs

Validated High-Throughput Screening

Sygnature Discovery has deployed its TMEM175 screening cascade to successfully identify a diverse range of modulators with clear, concentration-dependent effect.

Our success supports the platform’s ability to:

  • Detect subtle functional changes across wild-type, LoF, and GoF variants
  • Quantify modulator activity with robust EC₅₀/IC₅₀ curves
  • Assess variant-specific activity profiles to support disease relevance

This validated screening platform enables the discovery of novel pharmacological tools to modulate TMEM175 — advancing efforts to restore lysosomal homeostasis and better understand the channel’s role in neurodegenerative disease mechanisms.

Electrophysiology current traces showing TMEM175 channel activity in response to increasing concentrations (1-30 uM) of the agonist DCPIB. Currents, evoked using 500 ms voltage ramp and step protocol from -80 mV to +80 mV, show dose-dependent enhancement compared to vehicle control (0.2% DMSO).

Figure 1: Representative TMEM175 current traces before (grey line) and during the presence of increasing concentrations of the agonist DCPIB (blue lines). Currents are evoked by a 500 ms ramp from -80 mV to +80mV, followed by a 500 ms step from -80 mV to +80 mV before returning to the holding potential of 0mV.

SSM Electrophysiology for Lysosomal Ion Channels

Complementing our automated patch clamp capabilities, Sygnature Discovery also offers solid-supported membrane (SSM)-based electrophysiology – an ideal approach for studying intracellular lysosomal ion channels such as TMEM175.

  • Reconstituted lysosomal membranes containing TMEM175
  • Both activators and inhibitors can be evaluated in high-throughput 96-well format
  • Orthogonal validation to support HTS findings and confirm organellar ion channel modulation
TMEM175 current traces measured on the SURFE2R N1 platform showing concentration-dependent activation in response to DCPIB.

Figure 2: Representative TMEM175 current traces measured in the presence of increasing concentrations of the agonist DCPIB (0.3-30 µM) using solid-supported membrane (SSM) electrophysiology platform.

Accelerate Your TMEM175 Discovery Program

Whether you are screening novel modulators, developing a fast-follower approach or characterizing effects on TMEM175 variants, Sygnature Discovery’s TMEM175 platform offers expertise, flexibility and quality to support your discovery needs.

Contact Syganture Discovery

To learn more about our services or to request a quote.

Case Study

A Multi-Platform Approach to TMEM175 Drug Discovery

TMEM175 is a novel, constitutively active ion channel involved in the regulation of lysosomal pH, lysosomal Δψ and autophagy. TMEM175’s significance lies not only in its physiological role but also in its therapeutic promise. 

A Multi-Platform Approach to TMEM175 Drug Discovery
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