TG5 is strongly expressed in the epidermal granular cells, where it cross-links a variety of structural proteins in the terminal differentiation of the epidermis to form the cornified cell envelope. Protein cross-linking by TG5 is vital for maintaining cell-cell adhesion between the outermost layers of the epidermis.

Transglutaminases (TGMs) represent a family of enzymes capable of stabilizing protein assemblies by gamma-glutamyl-epsilon-lysine crosslinks.

Pathology

 homozygous mutation of transglutaminase-5 (TGM5) in acral eeling skin syndrome (MIM.270300)

• An established, in vitro, biochemical cross-linking assay revealed that, although T109M is not pathogenic, G113C completely abolishes TG5 activity.
• Three-dimensional modeling of TG5 showed that G113C lies close to the catalytic domain, and, furthermore, that this glycine residue is conserved in all known transglutaminases, which is consistent with pathogenicity.