Notch2 is a gene with significant roles in multiple biological processes. It is expressed in many cell types within the hematolymphoid compartment and is part of the Notch signaling pathway, a cell-cell communication system. Notch2 is essential for the development of splenic marginal zone B cells, regulates dendritic cell differentiation in the spleen, and has roles in intestinal immunity, helper T-cell divergence, and cytotoxic T-cell activation [3].

In diseases, mutations in Notch2 are associated with various conditions. In diffuse large B-cell lymphoma (DLBCL), mutations can cause the protein to escape ubiquitin-dependent degradation, promoting chemoresistance [1]. In Alagille syndrome, pathogenic variants in Notch2, along with JAG1, can lead to this autosomal-dominant multisystem disorder [2,5]. In a rare non-small cell lung carcinoma with co-expression of TTF1 and p40, NOTCH2 mutations were detected, potentially offering new therapeutic possibilities [6]. In gastric adenocarcinoma, high NOTCH2 expression is associated with early-stage cancer, suggesting it could be a diagnostic target [8]. In hepatocellular carcinoma, neutrophil extracellular traps promote immune escape by up-regulating CD73 through Notch2 [4]. In addition, Notch2 sensitizes chondrocytes to the inflammatory response of tumor necrosis factor α [7].

In conclusion, Notch2 is crucial for normal immune cell development and function. Its dysregulation, as seen from studies on disease-associated mutations, contributes to the pathogenesis of various cancers, Alagille syndrome, and chondrocyte-related inflammatory responses. Understanding Notch2 through these disease-associated findings may provide new insights for targeted therapies.