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TMEM97

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All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.

Background

Transmembrane protein 97 (TMEM97) also known as MAC30, is a polytopic membrane protein containing four predicted transmémbrene α-helices and an approximate molecular mass of 20–24 kDa. Localised mostly in the endosomal and lysosomal compartments, with contributions also from plasma membrane (PM) and Golgi pool representations, TMEM97 has surfaced as a critical node of intracellular cholesterol trafficking and lipid homeostasis. Structural and pharmacological studies of TMEM97 have recently confirmed it to be the main binding component within sigma-2 receptor complex, which is a molecular target for synthetic ligands that selectively kill rapidly proliferating tumor cells. TMEM97 interacts with low-density lipoprotein receptor (LDLR) and Niemann-Pick type C1 (NPC1) protein to regulate cholesterol egress from late endosomes in the context of the endolysosomal network, made up for membrane composition, cell signaling, cellular metabolism adaptation. In oncogenic settings, TMEM97 expression is substantially overexpressed in breast carcinoma, non-small cell lung cancer (NSCLC), prostate adenocarcinoma and glioblastoma multiforme where it promotes survival, proliferation of tumor cells as well nullification of endoplasmic reticulum stress. Key bioinformatics analyses indicated TMEM97 regulates amyloid precursor protein processing and neuronal autophagic flux in the nervous system implicating its role neural degeneration Alzheimer disease pathogenesis. TMEM97 combines versatile lipid-regulatory functions with sigma-2 receptor pharmacology and a disease-associated expression profile, making it an exceptionally appealing target for radioligand tumor imaging as well as cholesterol-modulating therapeutics (either mechanistically complimentary to statins or non-statinal) plus precision oncology drug conduit.

Fig.1 TMEM97 subcellular localization and function. (OA Literature)Fig.1 σ2R/TMEM97 subcellular localization and function.1

TMEM97 Is A Versatile Endolysosomal Orchestrator

TMEM97 orchestrates multiple cellular programs that go beyond its original annotation as a meningioma-associated antigen:

  • Tumor Metabolism & Imaging Sentinel: TMEM97 is preferentially expressed by many solid tumors compared to the surrounding normal tissue, and this differential expression has been leveraged for identification of these tumor types as well as contributions in surgical margin definitions with radiolabeled sigma-2 ligands. Besides imaging utility, its enrichment in tumour cells associates with enhanced cholesterol biosynthesis and mevalonate pathway reliance, making it a metabolic weakness that can be targeted by therapeutic inhibition.
  • Cholesterol Homeostasis Modulator: TMEM97 contributes to cholesterol homeostasis by facilitating the intracellular transport of endolysosome-derived LDL-cholesterol from the lumenal compartment into cytoplasm, thus sustaining sufficient sterols for membrane degradation or biogenesis processes and potentially for steroid hormone synthesis, as well.
  • Therapeutic Biomarker & Drug Target: The TMEM97 sigma-2 receptor pharmacology has spurred the development of high-affinity ligands that mediate caspase-dependent and lysosomal membrane permeabilization killing pathways. Previously, TMEM97-targeted antibody-drug conjugates and small-molecule cholesterol transport blockers are moving forward through preclinical pipelines as new therapeutic agents for cancer treatment or neuroprotection.

TMEM97 Membrane Protein Product

We present a broad panel of full-length and engineered TMEM97 membrane protein preparations designed to support research on this endolysosomal transmembrane protein. Considering the importance of appropriate membrane topology and preservation of structural features relevant to ligand recognition and TMEM97-associated cholesterol biology, our platform provides membrane protein formats tailored to different experimental requirements. These preparations can support ligand-binding studies, protein interaction research, structural and biochemical characterization, and investigations of TMEM97-associated cholesterol transport mechanisms. Protein format, production conditions, quality-control specifications, and available functional characterization are determined according to the corresponding product data or individual project requirements. Our TMEM97 collection provides research-ready materials for applications such as ligand-binding analysis, assay development, and membrane protein studies.

TMEM97 Protein Product

Not finding the membrane protein product you need? Contact us to start your one-stop custom service!

TMEM97 Stable Cell Line Product

Physiologically relevant cellular platforms are important for investigating TMEM97-associated cholesterol trafficking and related cellular responses. Leveraging lentiviral- and transposon-based delivery approaches, we provide TMEM97 stable cell lines designed to support studies of TMEM97 expression, localization, ligand response, and endolysosomal lipid biology. Depending on project requirements, customized cell models incorporating selected variants, reporter systems, or appropriate controls can be discussed to address specific mechanistic questions. These platforms provide scalable research tools for investigating TMEM97-associated cholesterol homeostasis, evaluating small-molecule modulators, and supporting broader studies of endolysosomal lipid transport. Specific cell configurations, validation methods, and functional readouts are determined according to individual project requirements.

TMEM97 Stable Cell Line Product

Not finding the stable cell line product you need? Contact us to start your one-stop custom service!

TMEM97 Recombinant Antibody Product

Our complete library of sequence-defined high-affinity monoclonal antibodies allow you to customize your TMEM97 research, designed for the topology of this endolysosomal transmembrane protein. These antibodies are capable of binding to latent and active TMEM97 conformations, as well as glycosylation-dependent epitopes on the extracellular and intracellular loops. They are pre-validated for: TMEM97 Western Blotting (both reducing and non-reducing), ligand competition Direct ELISA, Flow cytometry of fixed/permeabilized tumor cells; as well as high-resolution immunofluorescence & confocal microscopy of endosomal/lysosomal compartments. The latter can be used to perform immunohistochemistry on paraffin-embedded tissue sections and take the advantage of being functional blocking receptor interfering reagents. This data enables assessment of TMEM97 - expression profile across diverse cancer cell types, intracellular trafficking and aid in the design therapeutic antibodies for oncological & neurodegenerative disorder treatment.

TMEM97 Recombinant Antibody Product

Not finding the recombinant antibody product you need? Contact us to start your one-stop custom service!

Product Features

  • High Purity & Activity: High purity and verified integrity for dependable downstream work.
  • Diverse Expression Systems: Choice of expression formats to match routine or specialized projects.
  • Species Reactivity: Products available for human, mouse, pig, and other species.
  • Validated Applications: Application-tested to deliver consistent signals across common lab workflows.
  • Superior Batch-to-Batch Consistency: Stringent quality controls to ensure low variability from batch to batch.
  • Customization Options: Tags/Labels/package Modifications available upon request.

Custom TMEM97 Membrane Protein and Antibody Discovery Services

In addition to our catalogue products, we also offer a complete hosted service for protein design and engineering with specific applications in difficult endolysosomal transmembrane proteins:

  • Production & Validation: Cloning of the synthesized optimized gene into an expression vector, plus small-scale expression trials to help determine the best expression conditions.
  • Custom Antibody Production: Produced via large-scale expression in mammalian/insect/cell culture or bacterial expression systems, purified in detergent or reconstituted into nanodiscs.
  • Engineered Cell Lines: Creation of stable cell lines that physiologically mimic endogenous TMEM97 expression and activity.
  • Functional Assessment Systems: Designing and executing assays to assess protein function and ligand binding.

Frequently Asked Questions (FAQ)

  1. Do your TMEM97 products need specific post-translational modifications?

    Our products will include the elements necessary for glycosylation and proper disulfide bond formation to support endolysosomal localization & ligand recognition.

  2. Do your TMEM97 products specifically recognize ligands only after the ligands are properly localized to endolysosomes?

    Yes, our TMEM97 products have been engineered to properly localize to endosomes and lysosomes in order for them respond appropriately (in a physiologically relevant manner) when exposed with sigma-2 ligands provided the presence of cholesterol.

  3. Is your TMEM97 reagents approved for clinical diagnosis testing of Niemann-Pick disease biomarker measurement, cholesterol storage disorder stage or neurodegenerative risk assessment?

    No, all reagents and services provided are designated solely for research purposes and cannot be used for diagnostic testing or therapeutic purposes.

  4. Do you have doxycycline-inducible TMEM97 stable cell lines for the temporal modeling of cholesterol egress initiation points, lysosomal membrane contact site formation and cancer cells proliferation kinetics?

    Yes, we have established stable lines where transcription of TMEM97 is regulated by a doxycycline-responsive promoter. This system allows for exactly timed initiation of expression at pre-determined time points and follow-up analysis of progressive filipin clearance, mTORC1 reactivation, and SREBP-2 target gene down-regulation with temporal resolution without the chronic cholesterol depletion or compensatory upregulation in HMG-CoA reductase that is a hallmark characteristic confounding constitutive overexpression systems.

Reference
  1. Stathopoulos, Alyssa, et al. "Transmembrane protein 97 (TMEM97): molecular target and treatment in age-related macular degeneration (AMD)." Biomolecules 15.9 (2025): 1228. Under Open Access license CC BY 4.0, without modification. https://doi.org/10.3390/biom15091228
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