From the landmark report of protein serotonylation on small GTPases in 2003 to the most recent discovery of serotonin-modified histone H3 leading to epigenetic changes, over the course of the past 20 years, there is still a cloud of mystery surrounding this rare post-translational modification, other than the fact that tissue transglutaminase, perhaps most famously known for its role in celiac disease, is the enzyme responsible for catalyzing this transamidation reaction. Here, TGM2 is linked to celiac disease.