CDSN encodes corneodesmosin, a desmosomal protein essential for epidermal barrier integrity and corneocyte adhesion 1. The protein functions as a component of desmosomes—intercellular junctions that mediate cell-cell adhesion and contribute to skin development and differentiation 1. CDSN plays a critical role in maintaining the cornified envelope and regulating corneocyte desquamation, the normal shedding of outer skin cells. Biallelic CDSN mutations cause autosomal recessive peeling skin disease (generalized superficial skin exfoliation), while monoallelic mutations result in autosomal dominant hypotrichosis simplex of the scalp (progressive hair loss) 2. These mutations disrupt desmosomal integrity, demonstrating the protein's essential function in both epidermal barrier maintenance and hair follicle physiology 1. CDSN has emerged as a significant susceptibility gene for multiple immune-mediated diseases. Mendelian randomization identified CDSN as a causal gene for psoriasis, asthma, autoimmune hypothyroidism, and Graves' disease 3. Proteomic analysis revealed that CDSN expression is modulated by mutations in other immune-related genes 3. Recent prospective cohort studies demonstrated that elevated CDSN levels associated with genetic variants predict psoriatic disease development with high specificity (AUC=0.80), and CDSN silencing reduced psoriasis-like lesions in vivo 4. Additionally, CDSN variants show association with Kawasaki disease susceptibility 5. These findings position CDSN as both a disease biomarker and potential therapeutic target for inflammatory skin and systemic conditions.