G proteins are ubiquitous molecules that couple cell surface receptors to intracellular effectors and mediate diverse physiological effects. Alterations in G proteins can lead to serious pathophysiological consequences by increasing or decreasing their activity. Examples include pseudohypoparathyroidism caused by a 50% reduction in the activity of the Gs protein, and secretory diarrhea caused by Vibrio cholerae exotoxin activating the Gs protein. Gain-of-function mutations can also activate G proteins and cause diseases like acromegaly and certain thyroid adenomas.