The sigma-2 receptor (σR) is a sigma receptor subtype that has attracted attention due to its involvement in diseases such as neurological diseases, neurodegenerative, neuro-ophthalmic and cancer. It is currently  under investigation for its potential diagnostic and therapeutic uses.
Although the sigma-2 receptor was identified as a separate pharmacological entity from the sigma-1 receptor in 1990, the gene that codes for the receptor was identified as TMEM97 only in 2017. TMEM97 was shown to regulate the cholesterol transporter NPC1 and to be involved in cholesterol homeostasis. The sigma-2 receptor is a four-pass transmembrane protein located in the endoplasmic reticulum. It has been found to play a role in both hormone signaling and calcium signaling, in neuronal signaling, in cell proliferation and death, and in binding of antipsychotics.