Abstract
The σ(1) and σ(2) receptors are enigmatic proteins that have attracted attention for decades due to the chemical diversity and therapeutic potential of their ligands. However, despite ongoing clinical trials with σ receptor ligands for multiple conditions, relatively little is known regarding the molecular function of these receptors. In this review, we revisit past research on σ receptors and discuss the interpretation of these data in light of recent developments. We provide a synthesis of emerging structural and genetic data on the σ(1) receptor and discuss the recent cloning of the σ(2) receptor. Finally, we discuss the major questions that remain in the study of σ receptors.