TGM1

Transglutaminase-1, abbreviated TGM1, is an enzyme in the epidermis encoded by the TGM1 gene. It is a calcium-dependent transglutaminase that catalyzes the formation of covalent cross-links between structural proteins during the terminal differentiation of keratinocytes, contributing to the formation of the cornified cell envelope that helps establish the skin barrier.

TGM1-mediated cross-linking stabilizes the outermost layer of the epidermis by linking proteins such as involucrin, loricrin, and other structural components to lipids. This cross-linked network strengthens the barrier against water loss and environmental agents, supporting skin integrity and protection.

Mutations in TGM1 are associated with autosomal recessive congenital ichthyosis (ARCI), including lamellar ichthyosis and nonbullous ichthyosis. Loss or reduction of transglutaminase-1 activity impairs cornified envelope formation, leading to defective barrier function and widespread scaling that is often evident at birth or in early infancy. The condition typically requires ongoing management of dry skin and scaling.

Genetics and clinical testing: TGM1 is one of several genes implicated in ARCI. Pathogenic variants in TGM1 can be identified through genetic testing, which supports diagnosis and informs inheritance risk counseling. The expression of TGM1 is largely epidermal, reflecting its role in skin barrier formation.

Diagnosis and management: Diagnosis relies on clinical features combined with genetic testing. Management is supportive and multidisciplinary, focusing on moisturization, emollients, keratolytics to reduce scaling, and, in some cases, systemic retinoids for severe disease. There is no curative therapy for TGM1-related ichthyosis as of now.