Loss of function of NHE3, a well-known effector, negatively regulated by GC-C, has also been linked to IBD-like pathologies in humans and mice models (57, 114, 115), indicating that the impairment of Na+ absorption shared by both activating GC-C and inactivating NHE3 mutations could be a pathogenic driver in IBD. The gene discussed is SLC9A3; the disease is irritable bowel syndrome.