HEYL is a basic helix-loop-helix (bHLH) transcription factor that belongs to the hairy and Enhancer-of-split related gene family with YRPW motif 1. As a transcriptional repressor, HEYL binds preferentially to canonical E box sequences and functions as a downstream effector of Notch signaling. The protein plays critical roles in cardiovascular development and neural differentiation. In human fetal neural stem cells, LSD1-mediated repression of HEYL expression is essential for neuronal differentiation, as HEYL overexpression inhibits neurogenesis 2. Importantly, HEYL demonstrates significant oncogenic properties in breast cancer through dual mechanisms: it promotes tumor angiogenesis by directly binding to and upregulating proangiogenic cytokines CXCL1/2/3 in cancer cells, while also contributing to neoangiogenesis when expressed in tumor endothelium 3. HEYL-deficient mice show impaired vessel development, confirming its role in angiogenesis 3. The gene maps to chromosome 1.3 and represents a potential therapeutic target, as combination therapy targeting HEYL-induced angiogenic factors with anti-VEGF treatment shows enhanced efficacy in breast cancer models 3.