SERPINB4 is a serine protease inhibitor belonging to the serpin family, sharing 92% amino acid identity with its paralog SERPINB3 but differing in substrate specificity due to variations in the Reactive Center Loop 1. Primary function involves modulating immune responses and protecting cells from cytotoxicity. In cancer, SERPINB4 upregulation is driven by STAT3, NF-κB, and AP1 transcriptional regulators downstream of ALK fusion oncogenes in NSCLC, promoting tumor cell survival while inhibiting natural killer cell-mediated cytotoxicity 2. In inflammatory skin diseases, SERPINB4 expression is induced by type 2 (IL-4/IL-13) and type 17 (IL-17/IL-22) cytokine signaling, serving as an emerging biomarker for disease severity and treatment response in psoriasis and atopic dermatitis 3. In atopic dermatitis specifically, SERPINB4 expression is regulated through WTAP-mediated m6A RNA modifications; its downregulation ameliorates TNF-α/IFN-γ-induced oxidative stress, inflammation, and apoptosis in keratinocytes 4. SERPINB4 acts as an autoantigen in eczematized psoriasis, a distinct subtype characterized by TH2/TH17 immune signatures 5. As squamous cell carcinoma antigen 2 (SCCA2), circulating levels show altered ratios in hepatocellular carcinoma 6, supporting its clinical utility as a diagnostic and prognostic biomarker across malignancies and inflammatory conditions.