In 2013, the International Union of General and Clinical Pharmacologycataloged S1R as a ligand-regulated non-opioid intracellular receptor.4 Since then, evidence has been provided supportingparticipation of S1R in various pathological conditions, such as pain,cardiovascular disease, cancer, drug addiction, or neurodegenerativedisorders.5−7 Consequently, although no apparent endogenous ligandhas been unambiguously identified, efforts have been made to developS1R compounds as therapeutic agents. This evidence concerns the gene TMBIM4 and cardiovascular disorder.