TG2 is a calcium-dependent enzyme that catalyzes the formation of covalent bonds between free amine groups in one protein and protein-bound glutamines of another,creating highly cross-linked protein complexes.TG2 is ubiquitous and most diverse member of the transglutaminase family of enzymes.TG2 are implicated in cell differentiation,receptor-mediated endocytosis,cell adhesion,and induction of apoptosis.Recently,a growing body of literature suggests that it could be closely related to the development of drug resistance.Its role in cancer biology is briefly reviewed in this paper.