Desmoglein (DSG)

Desmogleins are a family of calcium-dependent transmembrane glycoproteins that serve as critical components of desmosomes, providing mechanical strength and cell-cell adhesion in epithelial and cardiac tissues (UniProt). The family includes four isoforms (DSG1-4), with DSG1 and DSG3 being the primary autoantigens in pemphigus, a group of autoimmune blistering diseases characterized by acantholysis (NIH, 2021). DSG2 is ubiquitously expressed and is associated with arrhythmogenic right ventricular cardiomyopathy when mutated, while also serving as a receptor for certain adenoviruses (PubMed, 2012). In therapeutic development, DSG3 is targeted by chimeric autoantibody receptor T (CAAR-T) cells, which use the DSG3 extracellular domain to selectively eliminate autoreactive B cells (Payne et al., 2020). Additionally, recombinant proteins like JO-1 bind to DSG2 to trigger the transient opening of epithelial junctions, enhancing the delivery of chemotherapeutic agents in solid tumors (Beyer et al., 2012).

Other names

Desmoglein 1Desmoglein 2Desmoglein 3Desmoglein 4DSG1DSG2DSG3DSG4Desmosomal cadherinPemphigus antigen

Selective B-cell depletion via chimeric autoantibody receptor (CAAR) targeting (DSG3-CAART); junction opening via DSG2 binding to enhance drug penetration (JO-1); B-cell depletion via CD20 targeting (Rituximab); FcRn inhibition to reduce pathogenic IgG levels (Efgartigimod); and broad immunosuppression (Corticosteroids/Immunosuppressants).