The sigma-1 receptor (S1R) is a ligand-regulated endoplasmic reticulum chaperone protein and a target for innovative compounds for the treatment of neurodegenerative and inflammatory diseases, cancers and pain diseases. The SIGMA-1 EUROPE network will bring together disciplines and expertises across Europe to advance the exploration and identification of the role of S1R in physiology and pathologies, to design innovative S1R ligands for cellular biology and medicine, and ultimately to train Young Reserachers and Innovators to revise current views of the diseases, to think out-of-the-box and explore novel and innovative S1R-based therapeutic opportunities.