T-cadherin as a potential novel regulator of intestinal inflammation and fibrosis

T-cadherin (T-cad) is a non-canonical member of the cadherin superfamily with a distinguished structure of its glycosylphosphatidylinositol (GPI) anchor instead of transmembrane and cytoplasmic domains. This lends unique properties to and equips T-cad with dynamic mobility within the plasma membrane and extensive lateral interactions with signaling partners. Beyond its role as an adhesion molecule forming homophilic interactions, T-cad functions as a receptor for adiponectin and low-density lipoprotein (LDL), therefore playing an important role in regulating cellular processes such as proliferation, differentiation, and migration. These properties underscore its critical involvement in physiological and pathological processes, including central nervous system development, cancer progression, and cardiovascular disease. However, the role of T-cad in intestinal inflammation, injury, and fibrosis remains underexplored. This review highlights the structural and functional characteristics of T-cad, its binding partners, its expression and functions in various types of cells, tissues and organs, and its roles in health and disease. This review also speculates on its potential involvement in intestinal inflammation, particularly in stricturing Crohn’s disease.