The intestinal epithelium plays a central role in protecting against the development of colitis, and is disrupted in inflammatory bowel disease (IBD). It serves as the physical barrier that, when breached, allows luminal contents (i.e. bacteria, antigens) to stimulate inflammatory responses. Sprouty2 (SPRY2) is an intracellular regulator of growth factor receptor signaling that is downregulated in a compensatory response to inflammatory stimuli in cell lines and a mouse model of colitis. Additionally, mice with intestine-specific Spry2 deletion are protected against colitis and have elevated tuft and goblet cell numbers, cell types thought to protect the intestinal epithelium.