OPRK1 and major depressive disorder: The ability of agonists acting at the same GPCR to preferentially elicit different signaling pathways by stabilizing the receptor in a particular active conformational state is called “biased agonism” or “functional selectivity.” The discovery of this phenomenon offers a therapeutic alternative to conventional full KOR agonism, which provides effective analgesia but at the cost of significant side effects including dysphoria, sedation, anxiety, and depression.