NOTCH1 is a transmembrane receptor that functions as a critical regulator of cell-fate determination through ligand-activated signaling 1. Upon activation by membrane-bound ligands, NOTCH1 releases its intracellular domain (NICD), which forms transcriptional complexes with RBPJ to activate target genes 2. In development, NOTCH1 is essential for early human corticogenesis, regulating progenitor identity, radial glial cell maintenance, and proliferation 3. NOTCH1 is more stringently required for γδ T-cell development than αβ-lineage differentiation, operating through miR-17-mediated negative feedback on BCL11B 4. In disease contexts, NOTCH1 plays prominent pathogenic roles. Constitutive or hyperactivated NOTCH1 signaling drives colorectal and lung cancer progression through enhanced proliferation, migration, and invasive characteristics 5. In colorectal cancer, DUSP6-mediated dephosphorylation of NOTCH1-ICD increases its stability and transcriptional activity, promoting tumor growth and predicting poor survival 2. NOTCH1 amplification in cancer-associated fibroblasts suppresses DNA damage responses, expanding stromal populations that support tumorigenesis 6. In pancreatic cancer, GAS41-H2A.Z.2 complexes activate NOTCH1 signaling to promote stemness and gemcitabine resistance 7. NOTCH1 mutations are prevalent in T-cell acute lymphoblastic leukemia, making it an attractive therapeutic target 8. These findings highlight NOTCH1's dual role in normal development and cancer pathogenesis, supporting its potential as a therapeutic intervention point across multiple malignancies.