DSG4 (desmoglein 4) encodes a transmembrane glycoprotein that functions as a critical component of desmosomes in hair follicles, mediating cell-cell adhesion between keratinocytes 1. The protein anchors to intermediate keratin filaments through interactions with plakoglobin and maintains proper hair follicle structure and barrier function 1. DSG4 plays an essential role in hair development, with mutations causing autosomal recessive forms of monilethrix and hypotrichosis characterized by sparse, fragile hair with beaded appearance 23. Pathogenic variants lead to dysfunctional protein that accumulates in the endoplasmic reticulum, loses affinity for plakoglobin, and undergoes ER-associated degradation, triggering unfolded protein response and ER stress 3. Transmission electron microscopy of affected hair shows fewer desmosomes, abnormal keratinization, and notable dysadhesion between outer root sheath cells 34. DSG4 mutations result in reduced desmosomal integrity, leading to hair shaft abnormalities including cuticle detachment, warping, and structural defects 4. The gene is downregulated in alopecia areata lesions alongside other hair follicle structural proteins, suggesting broader involvement in hair follicle biology 5. Clinical manifestations include hypotrichosis affecting scalp, eyebrows, and eyelashes, often accompanied by follicular hyperkeratotic papules 46.