Sprouty2 (Spry2) is an inflammation-responsive regulator of intracellular signaling that is suppressed in colitis. Loss of Spry2 levels leads to increased colonic tuft and goblet cell numbers; cell types protective against injury and infection. In particular, goblet cells produce host defense peptides (HDPs) which can enhance barrier effectiveness and limit pathogen colonization. While the activity of these cells is regulated and responsive to environmental cues, the precise mechanisms driving functional changes in goblet cells are largely unknown.