Sigma intracellular receptor 2 (Sigma-2R)

The Sigma-2 receptor, molecularly identified as Transmembrane protein 97 (TMEM97), is a four-pass transmembrane protein primarily localized in the endoplasmic reticulum and plasma membrane [1, 7]. It plays a critical role in cellular cholesterol homeostasis by interacting with the Niemann-Pick C1 (NPC1) protein and the low-density lipoprotein receptor (LDLR) [2, 3, 7]. In oncology, the Sigma-2 receptor is highly overexpressed in proliferating tumor cells compared to quiescent cells, making it a valuable biomarker for cancer imaging and a target for pro-apoptotic agonists [1, 13, 15]. In neurology, it acts as a key mediator of amyloid-beta (Aβ) and alpha-synuclein oligomer toxicity; antagonists like CT1812 are being developed to displace these toxic aggregates from synapses to treat Alzheimer's disease [2, 4, 14]. Beyond these, it is involved in calcium signaling and autophagy, positioning it as a versatile target for various age-related and degenerative conditions [1, 5, 12].

Other names

TMEM97Transmembrane protein 97MAC30Meningioma-associated proteinS2R

Antagonism (e.g., CT1812) displaces amyloid-beta oligomers from neuronal synapses to provide neuroprotection in Alzheimer's disease [14]. Agonism (e.g., Siramesine, PB28) induces caspase-3-mediated apoptosis and inhibits proliferation in various cancer cell lines [1, 9, 10].