FLG2 (filaggrin 2) is a structural protein essential for epidermal barrier function and keratinocyte differentiation. It localizes to the cornified envelope and keratohyalin granules of the stratum corneum, where it mediates cell-cell adhesion and contributes to skin barrier mechanical integrity 12. FLG2 expression is dynamically regulated during wound healing, with downregulation observed during reepithelialization as part of the epidermal maturation process 3. In inflammatory skin conditions, FLG2 expression is suppressed by type-2 cytokines (IL-4, IL-13) and IL-22 through STAT-mediated pathways, while the transcription factor GATA3 positively regulates FLG2 expression in keratinocytes 456. FLG2 downregulation is a hallmark of both atopic dermatitis and psoriasis, contributing to barrier dysfunction 78. Mutations in FLG2 are associated with peeling skin syndrome 6 9. Recent evidence suggests FLG2 may serve as a serum biomarker for acute respiratory distress syndrome prognosis 10. These findings position FLG2 as a critical determinant of epidermal barrier integrity and a therapeutic target in filaggrinopathies and inflammatory skin diseases.