Over the past decades, many basic research and clinical investigations have been focused largely on the roles of estrogen, through two classical nuclear estrogen receptors, ESR1 and ESR2 (also called ERα and ERβ), in the regulation of physiological functions and the pathophysiology of diseases such as cardiovascular, kidney, nervous, reproductive, endocrine, and gastrointestinal disorders. Here, ESR2 is linked to digestive system disorder.