• GUCA2B’s peptide uroguanylin activates GC-C and cyclic GMP in epithelial cells containing metallothionein genes, guarding against free radicals and transporting and storing metals.• BEST4/OTOP2 cell which expresses uroguanylin, identified.According to the research, IBD and colorectal cancer cases have lower levels of uroguanylin-producing colonic epithelial cells. Here, OTOP2 is linked to colorectal cancer.