FLG encodes filaggrin, a critical structural protein essential for epidermal barrier function and terminal keratinocyte differentiation 1. The protein aggregates keratin intermediate filaments and serves as a source of natural moisturizing factor (NMF) components including pyrrolidone carboxylic acid and urocanic acid 23. FLG expression is tightly regulated by inflammatory cytokines, with IL-4, IL-13, IL-17A, and IL-22 inhibiting its expression through STAT6 and STAT3 pathways, while aryl hydrocarbon receptor (AHR) activation upregulates FLG expression 45. Loss-of-function mutations in FLG are major predisposing factors for ichthyosis vulgaris and atopic dermatitis, with different mutation spectra observed across populations 6. FLG deficiency results in compromised epidermal barrier function, demonstrated by increased transepidermal water loss and altered stratum corneum structure 1. Environmental factors like particulate matter can suppress FLG expression through TNF-α and AHR-dependent mechanisms, contributing to barrier dysfunction 2. The IL-13-OVOL1-FLG axis is particularly important in atopic dermatitis pathogenesis, making IL-13 blockade a successful therapeutic approach 5. Beyond skin diseases, FLG mutations have been associated with increased tumor mutation burden in prostate cancer 7.