This study investigates the relationship between filaggrin expression and atopic dermatitis (AD) in patients without known filaggrin mutations. Filaggrin is a key protein in the cornified cell envelope (CCE), which is crucial for skin barrier function. The study found that filaggrin expression was significantly reduced in acute AD skin compared to normal skin, with further reduction observed in lesions from patients heterozygous for the 2282del4 mutation. Filaggrin expression was also reduced in keratinocytes differentiated in the presence of Th2 cytokines IL-4 and IL-13. The results suggest that the atopic inflammatory response modulates filaggrin expression, contributing to the skin barrier defect in AD. Neutralizing IL-4 and IL-13 could potentially improve skin barrier integrity, which may help prevent the progression to asthma in AD patients.This study investigates the relationship between filaggrin expression and atopic dermatitis (AD) in patients without known filaggrin mutations. Filaggrin is a key protein in the cornified cell envelope (CCE), which is crucial for skin barrier function. The study found that filaggrin expression was significantly reduced in acute AD skin compared to normal skin, with further reduction observed in lesions from patients heterozygous for the 2282del4 mutation. Filaggrin expression was also reduced in keratinocytes differentiated in the presence of Th2 cytokines IL-4 and IL-13. The results suggest that the atopic inflammatory response modulates filaggrin expression, contributing to the skin barrier defect in AD. Neutralizing IL-4 and IL-13 could potentially improve skin barrier integrity, which may help prevent the progression to asthma in AD patients.