Transmembrane protein 97 (Sigma-2 receptor) (TMEM97)

The Sigma-2 receptor, recently identified as Transmembrane protein 97 (TMEM97), is a four-pass transmembrane protein primarily localized in the endoplasmic reticulum and lipid rafts of the plasma membrane. It plays a critical role in regulating cholesterol homeostasis by interacting with the LDL receptor and the Niemann-Pick C1 (NPC1) protein, and it is also involved in modulating calcium signaling and autophagy. In oncology, the Sigma-2 receptor is highly upregulated in proliferating tumor cells, making it a valuable biomarker for tumor proliferation and a target for inducing apoptosis via sigma-2 agonists. In neurology, the receptor is a key target for Alzheimer's disease; antagonists like CT1812 are designed to block the binding of toxic Amyloid-beta oligomers to synapses, thereby preserving cognitive function. Its diverse involvement in cellular stress responses and lipid trafficking makes it a versatile therapeutic target across neurodegenerative, psychiatric, and oncological indications.

Other names

Sigma-2 receptorS2RMAC30Sigma-2 binding siteMeningioma-associated protein 30

Sigma-2 receptor ligands act as allosteric modulators or antagonists that can displace toxic protein aggregates like Amyloid-beta oligomers from neuronal receptors, or as agonists that trigger apoptotic pathways in rapidly proliferating cancer cells.