Protein-glutamine gamma-glutamyltransferase 1 (TGM1)

Protein-glutamine gamma-glutamyltransferase 1 (TGM1), also known as transglutaminase 1, is a membrane-bound enzyme primarily expressed in the suprabasal layers of the epidermis [1, 5]. It is essential for the formation of the cornified cell envelope, a critical component of the skin's protective barrier, by catalyzing the calcium-dependent cross-linking of structural proteins and the attachment of long-chain ceramide lipids [1, 17]. This process ensures the structural integrity and water-impermeability of the stratum corneum [1, 12]. Mutations in the TGM1 gene result in a loss of enzyme function, leading to autosomal recessive congenital ichthyosis (ARCI), a severe skin disorder characterized by thick, dark scales and impaired barrier integrity [10, 17]. In contrast, TGM1 is often upregulated in conditions like psoriasis and certain cancers, where it may promote keratinocyte hyperproliferation or tumor cell invasion [5, 6, 25]. Therapeutic strategies for TGM1-deficient patients include gene therapy (such as KB105) and enzyme replacement to restore function [10, 16, 20]. Conversely, research into TGM1 inhibitors aims to address its pathological roles in inflammation and malignancy [5, 27]. The enzyme's rapid turnover and the potential for immune responses against replacement therapies present significant therapeutic challenges [16, 23]. Overall, TGM1 is a pivotal target for both regenerative medicine in rare skin diseases and targeted therapy in oncology and dermatology [5, 29].

Other names

Transglutaminase 1TGase-1TGKEpidermal transglutaminaseTransglutaminase KTG(K)Protein-glutamine gamma-glutamyltransferase K

Restoration of enzyme activity via gene therapy or enzyme replacement; inhibition of transglutaminase-mediated cross-linking in hyperproliferative or invasive states.