SPDEF (SAM pointed domain containing ETS transcription factor) is an epithelium-specific ETS transcription factor that plays critical roles in epithelial cell differentiation and mucus barrier function 1. The protein functions as a key regulator of goblet cell differentiation and mucin production, particularly in respiratory and intestinal epithelia 23. SPDEF is essential for IL-13-induced mucostasis in bronchial epithelial cells, where its disruption abolishes IL-13-induced MUC5AC expression and goblet cell differentiation, preventing impairment of mucociliary clearance 2. In the intestine, SPDEF serves as a goblet cell marker gene and is involved in macrophage-mediated regulation of mucin-2 production and epithelial barrier integrity 3. The transcription factor exhibits dual roles in cancer, functioning as either a tumor promoter or suppressor depending on cancer type 4. In prostate cancer, SPDEF has been identified as a potential biomarker for castration-resistant prostate cancer progression 5. Additionally, SPDEF expression has been detected in pancreatic intraductal papillary mucinous neoplasms, particularly in borderline cases alongside gastric neck cell markers 6. During brain development, SPDEF is highly expressed in the subcommissural organ and plays a role in proper neuronal development 7.