LSR (lipolysis stimulated lipoprotein receptor), also known as angulin-1, is a tricellular tight junction protein that plays dual roles in epithelial barrier maintenance and cancer progression. LSR localizes to tricellular tight junction contacts where it colocalizes with tricellulin to maintain epithelial barrier function 1. In endometrial cancer, LSR expression decreases with cancer grade progression, and its suppression promotes malignancy through activation of Yes-associated protein (YAP) signaling, leading to increased cell migration and invasion 1. Similarly, in lung adenocarcinoma, downregulation of LSR induces malignant behavior through EGF-dependent claudin-2 upregulation and TGF-β-dependent metabolic changes 2. LSR expression is altered in a menstrual cycle-dependent manner in normal endometrial tissue, and these alterations are disrupted during endometrial cancer progression 3. The protein functions by recruiting other tight junction molecules like tricellulin to tricellular contacts, and its loss leads to epithelial barrier dysfunction associated with cancer progression and metastasis 3. LSR represents a critical regulator of epithelial integrity whose dysfunction contributes to cancer malignancy through multiple signaling pathways.