During the years Amino Acids have dedicated much attention to the transglutaminase (Tgase) field and this special issue is therefore the fifth of a series. In a previous occasion, we celebrated the 50 years from transglutaminase discovery with the editorial “An overview of the first 50 years of transglutaminase research” (Beninati et al. 2009). Following ideally from that point, we have now chosen as general theme for this issue the multiple roles played by type 2 transglutaminase as a multi-face protein. Most people are accustomed to analyze events and facts by taking into account objects and their opposite to get the whole, as in the case of light and darkness, day and night, or black and white as within a chessboard. This is also the case for type 2 transglutaminase (Tgase2): to get the complete picture we must examine both sides of the problem, the protein with its opposite activities, the involvement in cells and tissues leading either to cell growth/differentiation or conversely to cell death/atrophy, and their implications in health protection and pathology. The aim in launching this special issue was to contribute to settle these topics and we introduce now these general concepts dividing ideally the path in the steps mentioned above.
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