We are exploring the function of RNF43 in intestinal homeostasis using our mouse models bearing mutations in Rnf43. As chronic inflammation is a major contributor to CRC, we are also assessing its tumor suppressive function in different infection-driven colitis mouse models. By systematically analyzing changes in the stem cell compartment, the immune responses to bacterial infection, microbiota alterations, and activation of oncogenic signaling pathways, we aim at deciphering the contribution of RNF43 mutations to colorectal carcinogenesis. Complementary studies ongoing in human cohorts are ongoing in parallel to confirm the findings derived from our animal models.