Sulfation is a conjugation reaction essential for numerous biochemical and cellular functions in mammals. The 3′-phosphoadenosine 5′-phosphosulfate (PAPS) synthase 2 (PAPSS2) is the key enzyme to generate PAPS, which is the universal sulfonate donor for all sulfation reactions. The goal of this study is to determine whether and how PAPSS2 plays a role in colitis and colonic carcinogenesis.