HEY1 is a basic helix-loop-helix transcriptional repressor that functions as a key downstream effector of Notch signaling. It binds preferentially to canonical E-box sequences (5'-CACGTG-3') 1 and represses transcription by inhibiting cardiac activators GATA4/GATA6 and neuronal factors ASCL1/NEUROD4 2. In developmental contexts, HEY1 is essential for cardiovascular development, specifically regulating endocardial epithelial-to-mesenchymal transition required for cardiac valve and septum formation 3. The protein also maintains neuronal precursor cell fate and promotes angiogenesis regulation through reversible SUMOylation, where TRIM28-mediated SUMOylation facilitates HEY1 homodimer formation and DNA-binding capability to suppress angiogenic genes, while deSUMOylation permits heterodimerization with HES1, reducing transcriptional activity 4. In pathological contexts, HEY1 contributes to cancer stem cell maintenance through NOTCH1-HEY1 signaling activation in breast cancer 5 and participates in glioblastoma radioresistance via the circATIC/miR-520d-5p/Notch2-Hey1 axis 6. Additionally, HEY1-NCOA2 fusion genes characterize mesenchymal chondrosarcoma, correlating with elevated COL2A1 and Bcl2 expression 7. These findings establish HEY1 as a critical transcriptional regulator with diverse roles spanning developmental processes and oncogenic pathways.