reasons for these effects are not well understood, even though σ1 receptors have been linked circumstantially to a wide variety of signal transduction pathways. Links between σ1 receptors and G-proteins have been suggested such as σ1 receptor antagonists showing GTP-sensitive high-affinity binding; there is also, however, some evidence against a G-protein coupled hypothesis. The σ1 receptor has been shown to appear in a complex with voltage gated K+ channels (Kv1.4 and Kv1.5), leading to the idea that σ1 receptors are auxiliary subunits. σ1 receptors apparently co-localize with IP3 receptors on the endoplasmic reticulum where theymay be involved in preventing endoplasmic reticulum stress in neurodegenerative diseases. Also, σ1 receptors have been shown to appear in galactoceramide enriched domains at the endoplasmic reticulum of mature oligodendrocytes. The wide scope and effect of ligand binding on σ1 receptors has led some to believe that σ1 receptors are intracellular signal transduction amplifiers. Recently, σ1R has been implicated in autophagosome formation and maturation. Autophagy is a broad homeostatic, metabolic, cytoplasmic quality control, and metabolic process affecting many functions in the cell. σ1R is targeted by the nsp6 protein of SARS-CoV-2 to inhibit autophagosome formation as a process competing with the coronavirus for cellular endomembranes that the virus needs for its own replication. This along with the observed beneficial effects of sigma-1 receptor agonist and SSRI fluvoxamine in patients with SARS-COV-2 infection has led to the hypothesis that the sigma-1 receptor could be a target for the treatment of SARS-COV-2. There has been much interest in the sigma-1 receptor and its role in age-related neurodegenerative diseases such as Alzheimer's disease. During healthy ageing, the density of sigma-1 receptors has been to increase. However, in diseases such as Alzheimer's disease, there appears to be a reduction in sigma-1 receptor expression. It has been suggested that targeting the sigma-1 receptor along with other receptors could increase neuron survival and function in neurodegenerative disease. The activation of autophagy has also been suggested as a downstream mechanism linked to sigma-1 receptor activation. Knockout mice σ1 receptor knockout mice were created in 2003 to study the effects of endogenous DMT. Strangely, the mice demonstrated no overt phenotype. As expected, however, they did lack locomotor response to the σ ligand (+)-SKF-10,047 and displayed reduced response to formalin induced pain. Speculation has focused on the ability of other receptors in the σ family (e.g., σ2, with similar binding properties) to compensate for the