MUC21 is a transmembrane mucin protein that functions as a cell surface-associated glycoprotein with diverse roles in cellular protection and tumor progression. The protein consists of a mucin domain with 28 tandem repeats, a stem domain, transmembrane region, and cytoplasmic tail 1. MUC21 serves multiple protective functions, including conferring resistance to apoptosis in an O-glycosylation-dependent manner, where T-antigen glycan structures with or without sialic acid are essential for its antiapoptotic effects 2. In normal tissues, MUC21 is expressed in lung, large intestine, thymus, and testis, with specific localization to bronchial and bronchiolar epithelia 1. However, MUC21 exhibits significant pathological roles in cancer progression. It promotes tumor cell survival and metastasis through multiple mechanisms: activating STAT3/AKT pathways in glioblastoma 3, regulating SLITRK5 and hedgehog signaling in melanoma 4, and facilitating perineural invasion in pancreatic cancer through GDNF-induced phosphorylation and RAC2 activation 5. Notably, MUC21 functions as an immunosuppressive ligand that enables cancer cells to evade NK and T cell-mediated cytotoxicity by creating steric hindrance 6. These findings establish MUC21 as both a prognostic marker and potential therapeutic target across multiple cancer types.