Characteristic features of human MVID were observed in our cMYO5BKO mice including weight loss, severe diarrhea, brush border defects in villus enterocytes of the small intestine, pathognomonic microvillus inclusions (MIs), widened spaces between enterocytes, apical trafficking defects of ion transporters including DRA, NHE3, and reduced expression of the glucose transporter SGLT1. Here, SLC26A3 is linked to microvillus inclusion disease.