TGM2 and neoplasm: TG2 has been identified as an important extracellular crosslinking enzyme involved in ECM turnover.24, 25, 26, 27 In contrast, TG2 is secreted into ECM and forms a hetero complex with its high-affinity binding partner fibronectin (FN) through its N-terminal 42-kD fragment in a crosslinking activity-independent manner.28, 29 The TG–FN complex promotes FN fibril deposition and RGD-independent cell adhesion via syndecan-4/2 and α5β1 integrin co-signaling,29 and sustains cell survival in osteoblasts,30 bone marrow-derived mesenchymal stem cells,31 and many tumor cells.32, 33