Abstract: Secreted FXYD family proteins are expressed by intestinal mucosa and/or associated tissues to regulate cell production in intestinal crypts in response to tissue damage. Such tissue damage may arise from disease, exposure to injurious chemicals (e.g., due to poisoning, chemotherapy, chemical weapons), or exposure to injurious radiation (e.g., due to nuclear power accidents, radiological weapons, radiation therapy). Because these proteins are secreted in response to epithelial tissue damage, some of them are implicated in tissue repair response or an inflammatory response which prolongs or exacerbates the tissue damage. Examples of these proteins include FXYD 3, FXYD 4, and FXYD 5. Diagnostic methods based upon the role of the FXYD proteins in epithelial tissue damage are disclosed.