Our study demonstrated an important role of Fam3D in supporting the development of the normal architecture of mouse colon in which the absence of the molecule is associated with abnormal development of the colon crypts, increased spontaneous low-level inflammation, reduced secretory function of goblet cells causing thinner layer of protective mucins on the mucosal surface as well as a reduction in key anti-microbial molecules, culminating in dysbiosis, which exacerbates the colitis with markedly increased incidence of cancer. Here, FAM3D is linked to colitis.