TIE1, an endothelial receptor-tyrosine-kinase, plays a crucial role in vascular development and remodeling, including in diseases such as diabetic retinopathy (DR). However, the molecular mechanisms and regulatory interactome governing TIE1 function remain largely unknown in endothelial biology. This study was designed to identify long noncoding-RNA (lncRNA) regulators of TIE1 and to elucidate their functional roles in endothelial biology. Through integrative screening and functional assays, we discovered a novel lncRNA, TIE1-associated angiogenic lncRNA (TAAL), that modulates TIE1 function and signaling during vascular-remodeling. Further analyses revealed that dysregulation of the TAAL–TIE1-axis is associated with pathological vascular changes observed in DR, highlighting its potential relevance to disease progression.