Notch1 is a transmembrane receptor protein that plays a critical role in various cellular processes, including cell fate determination, differentiation, and proliferation. It is part of the Notch signaling pathway, which is highly conserved in mammals and is involved in multiple developmental processes and diseases, particularly in the immune system and cancer. In the context of mouse models, Notch1 is essential for the development of T cells and is frequently mutated in T-cell acute lymphoblastic leukemia (T-ALL). Activating mutations in Notch1 can lead to the development of T-ALL by causing ligand-independent activation of the receptor, resulting in constitutive signaling and uncontrolled cell proliferation. These mutations often occur in the heterodimerization (HD) domain of Notch1, which is responsible for preventing spontaneous activation in the absence of ligand. Notch1 signaling is also implicated in the pathogenesis of other cancers, such as breast cancer. In the case of BRCA1 deficiency, Notch1 activation can compensate for the loss of BRCA1 and promote the formation of triple-negative breast cancer (TNBC). This occurs through the activation of the epithelial-mesenchymal transition (EMT) signaling pathway, which is involved in the progression of TNBC.