This is the third special issue focused on "Transglutaminases" that is now available on this journal and dedicated to one of the pioneers of these enzymes, John Edward Folk, who died December 2010 [see in this issue Beninati et al. 2012a]. The first edition, "Polyamines and Transglutaminases" was published in Amino Acids, vol 26, no. 4, 2004, with the contribution of two prestigious Guest Editors as Alberto Abbruzzese and Mauro Piacentini. This editorial initiative was followed by the second special issue published in occasion of the 50th years of the discovery of transglutaminase. Indeed, "Transglutaminase 2: 50th Anniversary of the Discovery" Amino Acids, vol 36, no. 4, 2009, was published with the valuable collaboration of Carlo Maria Bergamini and Mauro Piacentini (Beninati et al. 2009). To continue with this editorial tradition, on this occasion, an outstanding board of Guest Editors composed by Francesco Facchiano and Mauro Piacentini has also been invited to promote this initiative and recruit a selected panel of Authors, many of who participated in the first and second edition of the Gordon Conference on Transglutaminases: "Transglutaminases in Human Diseases Processes" chaired by Rickard L Eckert and Kapil Mehta on July 18-23, 2010, and by Kapil Mehta and Mauro Piacentini on July 15-20, 2012, held at Davidson College, NC, USA. In this Amino Acids special issue, the manuscripts were selected to reflect the progress and the future perspectives of transglutaminases.