Protein-glutamine gamma-glutamyltransferase 5 (TGM5)

Protein-glutamine gamma-glutamyltransferase 5 (TGM5) is a calcium-dependent enzyme mainly expressed in the epidermis where it catalyzes the formation of isopeptide bonds (cross-links) between glutamine and lysine residues in structural proteins[1][2][3][4][6][7]. This cross-linking process is essential for the formation and stabilization of the cornified cell envelope, which is critical for skin barrier function and mechanical resilience. Mutations in TGM5 reduce or abolish its enzymatic activity and are causative for acral peeling skin syndrome, a genodermatosis characterized by the painless peeling of the outermost layers of the epidermis, especially on the hands and feet[2][3][4]. TGM5 biology is most relevant in keratinocyte differentiation and skin homeostasis, and its dysfunction has not been directly linked to other major disease categories or targeted by currently approved drugs.

Other names

Transglutaminase 5TG5Transglutaminase XTGXTGase-5TGase XTransglutaminase Vprotein-glutamine gamma-glutamyltransferase 5 isoform 1protein-glutamine gamma-glutamyltransferase 5 isoform 2PSS2TGASE5TGASEX

Enzyme inhibition or modulation (theoretical for drugs; no approved drugs known)