DSG1 (desmoglein 1) is a transmembrane glycoprotein component of intercellular desmosome junctions that mediates cell-cell adhesion in stratified epithelium 1. It functions by interacting with plaque proteins and intermediate filaments to establish adhesive contacts 2. DSG1 is specifically expressed in stratified epidermis and requires proper plasma membrane localization via retromer-mediated endosomal recycling to promote keratinocyte stratification and epidermal regeneration 3. The protein exhibits a dynamic Dsg1/Dsg3 ratio across epidermal layers, with increasing ratios from basal to granular layers, and exists both within desmosomes and in extradesmosomal complexes 4. DSG1 mutations cause palmoplantar keratoderma, with identified disease-causing variants in multiple families 5. In pemphigus vulgaris, autoantibodies against DSG1 (and DSG3) disrupt desmosome assembly and composition 4, with anti-DSG1 antibody levels serving as relapse predictors in rituximab-treated patients 6. Neonatal pemphigus can result from transplacental maternal anti-DSG1 antibodies, though the condition typically resolves within weeks 7. DSG1 deficiency also affects epidermal metabolism through altered GLUT1 transporter expression 3. These findings establish DSG1 as critical for maintaining epidermal barrier function and intercellular integrity.