Transglutaminases (Tgases) are a group of enzymes that catalyze the post-translational modification of proteins by forming isopeptide bonds. These enzymes can cross-link proteins through ε-(γ-glutamyl)lysine bonds or incorporate primary amines at selected glutamine residues. Cross-linked products are highly resistant to mechanical and proteolytic degradation and are found in various tissues, including skin, blood clotting, and wound healing. However, deregulation of Tgase activity is associated with diseases such as chronic neurodegeneration, cancer, and autoimmune disorders. Tgases are involved in various physiological processes, including cell adhesion, wound healing, and extracellular matrix stabilization. They are also involved in the pathogenesis of diseases like coeliac disease, where they contribute to the formation of immunogenic aggregates. Tgases are regulated by calcium and other factors, and their activity is crucial for maintaining cellular homeostasis. The enzyme has multiple isoforms, with type 2 Tgase being the most studied. It is involved in various cellular functions, including cell death and the stabilization of the extracellular matrix. Tgases are also used in biotechnology for their ability to modify proteins and act as biological glues. The study of Tgases has led to a better understanding of their roles in health and disease, and their potential applications in biotechnology.Transglutaminases (Tgases) are a group of enzymes that catalyze the post-translational modification of proteins by forming isopeptide bonds. These enzymes can cross-link proteins through ε-(γ-glutamyl)lysine bonds or incorporate primary amines at selected glutamine residues. Cross-linked products are highly resistant to mechanical and proteolytic degradation and are found in various tissues, including skin, blood clotting, and wound healing. However, deregulation of Tgase activity is associated with diseases such as chronic neurodegeneration, cancer, and autoimmune disorders. Tgases are involved in various physiological processes, including cell adhesion, wound healing, and extracellular matrix stabilization. They are also involved in the pathogenesis of diseases like coeliac disease, where they contribute to the formation of immunogenic aggregates. Tgases are regulated by calcium and other factors, and their activity is crucial for maintaining cellular homeostasis. The enzyme has multiple isoforms, with type 2 Tgase being the most studied. It is involved in various cellular functions, including cell death and the stabilization of the extracellular matrix. Tgases are also used in biotechnology for their ability to modify proteins and act as biological glues. The study of Tgases has led to a better understanding of their roles in health and disease, and their potential applications in biotechnology.