The mucosal surface of the intestine comprises epithelial monolayer cells that are critical for the absorption of nutrients and defense against a variety of organisms or toxins. Aging epithelial cells must be rapidly replaced by younger cells for the maintenance of normal function. However, details of the underlying mechanism governing the rapid turnover of intestinal epithelial cells have remained largely unknown. Recently, we found a novel enzyme, designated membrane-type serine protease 1 (MT-SP 1), and suggested that it is a key molecule for control of intestinal epithelial turnover under physiological conditions. Moreover, we found that pancreatic secretory trypsin inhibitor (PSTI) inhibits granzyme A (GrA), which is likely to induce apoptosis of abnormal intestinal epithelial cells. These results suggest that intestinal epithelial cells themselves produce proteases such as MT-SP 1 that can regulate turnover of the intestinal epithelium, and that the pathological cell turnover mediated at least partly by GrA can be controlled selectively with substances such as PSTI.