JAG2 (jagged canonical Notch ligand 2) functions as a crucial Notch pathway ligand that regulates cell differentiation, immune responses, and disease pathogenesis. JAG2 serves as a ligand for Notch receptors, activating downstream signaling cascades that control cellular fate decisions 1. In cancer contexts, JAG2 demonstrates dual roles depending on tumor type. In non-small cell lung cancer, JAG2 promotes immune evasion by suppressing anti-tumor T cell responses and maintaining immunosuppressive macrophage phenotypes 2. Similarly, in high-grade serous ovarian cancer, JAG2-positive tumor-associated neutrophils create an immunosuppressive microenvironment by promoting regulatory T cell differentiation through RBPJ-mediated Notch signaling activation 3. Conversely, in endometrial cancer, JAG2 appears to have tumor-suppressive functions, with significantly reduced protein levels observed in stage IB adenocarcinomas compared to healthy tissue 4. JAG2 also contributes to cancer stem cell maintenance, as demonstrated in hepatocellular carcinoma where CD146-mediated JAG2 upregulation enhances stemness and chemoresistance through Notch pathway activation 5. Clinically, JAG2 expression correlates with patient outcomes and represents a potential therapeutic target, with Notch inhibitors showing promise in overcoming immunotherapy resistance 32.