The predominant hypothesis that G protein signaling promotes the analgesic effects of opioids, while arrestin-3 engagement is detrimental and causes the respiratory depressive side-effects, arose from the finding that mice lacking arrestin-3 (Arr-3 KO) displayed reduced respiratory depression in response to morphine (a MOR agonist) [9]. The gene discussed is ARR3; the disease is Respiratory insufficiency due to muscle weakness.