Intestinal epithelial homeostasis depends on a tightly regulated balance between intestinal epithelial cell (IEC) death and proliferation. Disruption of factors that promote IEC death result in intestinal inflammation, whereas loss of anti-apoptotic proteins, such as BCL2 or its family member BCL2L1, has no effect on intestinal homeostasis in mice. We investigated the functions of the anti-apoptotic protein MCL1, another member of the BCL2 family, in intestinal homeostasis in mice.