Sigma receptors are divided into two main subtypes: sigma-1 (σ1) and sigma-2 (σ2), which are unique non-G protein-coupled receptors. The σ1 receptor is enriched on the endoplasmic reticulum membrane, while the precise molecular identity of the σ2 receptor has been identified more recently, being associated with the cell membrane and other organelles. These receptors participate in regulating various physiological and pathological processes, including neurotransmission, cell proliferation, neuroprotection, and cell death. Sigma receptors are expressed in the brain, liver, kidneys, and other organs, and are associated with various pharmacological effects, including antidepressant, anxiolytic, and neuroprotective properties. Specific expression and mutations of the σ1 receptor gene are associated with neurodegenerative diseases, cancer, and psychiatric disorders. Sigma receptors, due to their wide-ranging biological functions and pharmacological potential, have become important targets for drug development.