MUC17 is a membrane-bound mucin that serves as an essential component of the small intestinal glycocalyx, forming a dense protective barrier on the apical surface of enterocytes 1. This transmembrane mucin extends approximately one micrometer from the brush border and can shuttle between surface and intracellular vesicular localization, enabling enterocytes to detect and respond to bacterial challenges 1. Apical targeting of MUC17 is regulated by the motor proteins MYO1B and MYO5B and the sorting nexin SNX27, which control both MUC17 turnover and brush border localization 2. MUC17 protects against commensal and pathogenic bacterial contact with the epithelium, and its loss compromises the intestinal barrier, leading to increased bacterial translocation and development of disease-associated dysbiosis 3. Beyond intestinal homeostasis, MUC17 facilitates epithelial cell restitution and migration through EGF-like cysteine-rich domain-mediated ERK phosphorylation, promoting healing in experimental colitis models 4. Clinically, MUC17 dysregulation is associated with disease pathogenesis: reduced MUC17 levels occur in Crohn's disease 3, while MUC17 deletions and mutations negatively impact prognosis in biliary tract cancers and gliomas 56. These findings establish MUC17 as a critical region-specific mucosal defense component with significant therapeutic potential.