Transglutaminases (Tgase) are a group of enzymes responsible for catalyzing the cross-linking of protein molecules, creating stable covalent bonds. This family includes several members, such as tissue type (tTgase) and epidermal type (eTgase), with varying localizations and functions inside and outside cells. Tgase plays a crucial role in cell signaling, apoptosis, and the stabilization and remodeling of the extracellular matrix. The activity of these enzymes is strongly regulated by calcium ions. Gene expression of Tgase shows significant specificity across different tissues. Mutations or dysregulation of gene expression is associated with the development of various diseases, including fibrosis, neurodegenerative diseases, and cancer.