The beneficial role of GC-C signaling during IBD is implicated from the observation that human patients with IBD display a significant decrease in transcript levels of GUCA2A, GUCA2B, and GUCY2C, and loss of these proteins is linked with the severity of the disease in patients (Brenna et al., 2015; Lan et al., 2016). Here, GUCA2B is linked to inflammatory bowel disease.