CLDND1 (claudin domain containing 1) is a claudin-family homolog that localizes to tight junctions and regulates vascular permeability by negatively controlling cell permeability to small molecules 1. CLDND1 expression is transcriptionally regulated by RORα 2 and MZF1 3, while post-transcriptionally regulated by miR-124 4 and miR-595 5. Mechanistically, CLDND1 knockdown increases endothelial permeability 1 and induces caspase-dependent apoptosis in breast cancer cells through mitochondrial pathways 6. In oral squamous cell carcinoma, elevated CLDND1 associates with an immune-cold, ferroptosis-resistant phenotype and independently predicts worse overall survival (HR≈1.51) and disease-specific survival (HR≈1.61) 7. CLDND1 suppression enhances ferroptosis susceptibility by reducing GPX4 and SLC7A11 expression 7. In cerebrovascular disease, transient CLDND1 decrease after hemorrhage promotes vascular hyperpermeability 1, and low miR-124 levels correlate with elevated CLDND1 in stroke-prone hypertensive rats 4. In lung cancer, CLDND1 serves as a downstream effector in the miR-199a-3p/FTO/MZF1 regulatory axis 8. These findings position CLDND1 as a multifunctional tight junction protein with roles in vascular integrity, cancer progression, and therapeutic resistance.