Keratinocyte cell surface adhesion proteins

Keratinocyte cell surface adhesion proteins are a diverse group of transmembrane molecules, including desmogleins (DSG1, DSG3), desmocollins, E-cadherin, and integrins (e.g., alpha6beta4), that are essential for maintaining the structural integrity and barrier function of the skin. These proteins organize into specialized junctions such as desmosomes, adherens junctions, and hemidesmosomes to facilitate robust cell-cell and cell-matrix attachment. In autoimmune blistering diseases like pemphigus vulgaris and pemphigus foliaceus, these proteins are the primary antigens targeted by pathogenic autoantibodies, leading to the loss of intercellular adhesion known as acantholysis. Beyond their structural roles, they also function as signaling hubs that regulate keratinocyte proliferation, differentiation, and migration, making them relevant in wound healing and cancer. In oncology, the dysregulation of these proteins, particularly the loss of E-cadherin, is a hallmark of epithelial-to-mesenchymal transition (EMT) and metastasis. Therapeutic interventions primarily focus on managing autoimmune responses through B-cell depletion or FcRn inhibition, while experimental strategies include the use of mimetic peptides to stabilize adhesion and chimeric autoantibody receptor (CAAR) T cells to selectively deplete pathogenic B cells.

Other names

Keratinocyte adhesion moleculesDesmosomal proteinsEpidermal adhesion proteinsKeratinocyte cell-surface adhesion molecules

Reduction of pathogenic autoantibody titers through B-cell depletion or FcRn inhibition; stabilization of protein-protein trans-interactions using mimetic peptides; selective depletion of autoantibody-producing B-cell clones; suppression of the systemic immune response.