TGM1mediated

TGM1-mediated processes refer to the biological activities driven by transglutaminase 1 (TGM1). TGM1 is a calcium-dependent enzyme of the transglutaminase family that is anchored to the inner surface of the keratinocyte plasma membrane. During terminal differentiation of keratinocytes, rising intracellular calcium activates TGM1, enabling it to catalyze the formation of ε-(γ-glutamyl)lysine crosslinks between structural proteins including involucrin, loricrin, and small proline-rich proteins. Through these crosslinks, soluble proteins become covalently bound to the cell membrane, contributing to the assembly of the insoluble cornified envelope, the core component of the epidermal barrier.

TGM1-mediated crosslinking also stabilizes the cornified envelope and helps incorporate secreted lipids to form the lipid–protein barrier of the stratum corneum, providing mechanical resilience and water-retention properties. Its activity is tightly regulated in epidermis and is diminished in certain ichthyosis conditions.

Clinically, mutations in the TGM1 gene are a common cause of autosomal recessive congenital ichthyosis, particularly lamellar ichthyosis and congenital ichthyosiform erythroderma. Loss or reduction of TGM1 function impairs cornified envelope formation and barrier integrity, leading to scaling, erythema, and increased transepidermal water loss.

Research into TGM1-mediated processes informs understanding of skin differentiation, barrier disorders, and potential therapeutic approaches for ichthyoses and other keratinization disorders.