Sig1R (SIR) is a single transmembrane domain that crystallizes as a trimer. It resides in ER, nuclear and the MAM. The bulk of the protein resides within the cytosol. Efforts to understand its mechanisms of retinal neuroprotection have identified functions associated with ion channel regulation, chaperone activity, oxidative stress modulation and regulation of calcium. (Abbreviations: Sigma 1 Receptor (SIR), endoplasmic reticulum (ER), mitochondrial associated membrane (MAM), calcium (Ca2+)