Cells communicate through complex mechanisms that typically involve receptors and ligands that bind to them. Endogenous ligands, produced by the body, have been identified for the vast majority of cellular receptors, helping explain receptor existence and function. But in the case of sigma-1 receptors, which interact with a diverse array of psychoactive drugs, an endogenous ligand has remained elusive. Now, researchers at the Lewis Katz School of Medicine at Temple University (LKSOM), in collaboration with scientists at the University of Cambridge, show that choline, an essential nutrient that functions in metabolism, is an endogenous activator of sigma-1 receptors, marking an important advance in cell biology.