Due to sluggish contractility of gallbladder smooth muscles in gallstone patients and animal models of cholesterol gallstones, it is likely that the contractile mechanisms of gallbladder involve activation of phospholipase C by the CCKAR signaling pathway, leading to signal-transduction decoupling when cholesterol is largely accumulated in the sarcolemmal membrane of smooth muscles in the gallbladder [78,79,80,81,82,83,84]. The gene discussed is CCKAR; the disease is gallstones.