SERPINB3 (serpin family B member 3) is a serine/cysteine protease inhibitor that plays critical roles in immune modulation and cancer progression. The protein functions as a papain-like cysteine protease inhibitor and suppresses UV-induced apoptosis by inhibiting JNK1 activity 1. SERPINB3 mechanistically promotes tumor progression through multiple pathways: it activates STAT-dependent chemokine production (CXCL1, CXCL8, S100A8/A9) that recruits myeloid-derived suppressor cells and tumor-associated macrophages, thereby suppressing antitumor T cell responses 2. Additionally, SERPINB3 confers cuproptosis resistance by inhibiting FDX1 transcription through MAPK pathway activation, achieved by direct interaction with MEK1 and prevention of its autophagic degradation 3. The protein also promotes immune evasion by upregulating PD-L1 expression on tumor cells 3. Clinically, SERPINB3 serves as a biomarker for poor prognosis across multiple cancers including hepatocellular carcinoma and cholangiocarcinoma 45. In autoimmune contexts, SERPINB3 acts as an autoantigen in eczematized psoriasis, driving tissue-resident memory T cells and TH2-skewed inflammation 6. High serum SERPINB3 levels correlate with treatment resistance and poor patient outcomes 24.