The study by Jordan and Devi investigates the heterodimerization of opioid receptors, specifically the κ and δ receptors, and its impact on receptor function. They provide biochemical and pharmacological evidence that these two fully functional G-protein-coupled receptors (GPCRs) can form a heterodimer, which exhibits distinct ligand binding and functional properties compared to either receptor alone. The κ-δ heterodimer shows synergistic binding to highly selective agonists and potentiates signal transduction, suggesting a novel mechanism for modulating receptor function. The study also highlights the role of disulfide bonds in receptor dimerization and the potential for heterodimerization to form new receptor subtypes, which could be targets for endogenous opioid peptides. These findings contribute to our understanding of how GPCRs are regulated and provide potential targets for therapeutic drug development.The study by Jordan and Devi investigates the heterodimerization of opioid receptors, specifically the κ and δ receptors, and its impact on receptor function. They provide biochemical and pharmacological evidence that these two fully functional G-protein-coupled receptors (GPCRs) can form a heterodimer, which exhibits distinct ligand binding and functional properties compared to either receptor alone. The κ-δ heterodimer shows synergistic binding to highly selective agonists and potentiates signal transduction, suggesting a novel mechanism for modulating receptor function. The study also highlights the role of disulfide bonds in receptor dimerization and the potential for heterodimerization to form new receptor subtypes, which could be targets for endogenous opioid peptides. These findings contribute to our understanding of how GPCRs are regulated and provide potential targets for therapeutic drug development.