DCBLD2 (discoidin, CUB and LCCL domain containing 2) is a transmembrane protein that functions as a key regulator of cellular signaling pathways and receptor endocytosis. The protein acts as a modulator of PDGFR-β endocytosis in vascular smooth muscle cells by interacting with Caveolin-1, preventing excessive receptor internalization and thereby controlling vascular hyperplasia 1. DCBLD2 serves as a downstream target of EGFR signaling, undergoing tyrosine phosphorylation in response to EGF stimulation 2. The protein plays complex roles in cancer biology, where its dysregulation contributes to malignant progression through multiple mechanisms. In breast phyllodes tumors, DCBLD2 interacts with CD146 to activate the PI3K/AKT pathway, promoting tumor growth 3. In glioblastoma, elevated DCBLD2 expression correlates with poor prognosis and enhances epithelial-mesenchymal transition by modulating E-cadherin, vimentin, and transcription factors like Snail and Twist 4. Conversely, DCBLD2 functions as a tumor suppressor in gastric cancer, where its expression is frequently downregulated through promoter hypermethylation, and restoration inhibits cell proliferation and invasion 5. The protein is also regulated by miR-451a in papillary thyroid cancer 6 and represents a potential therapeutic target, as demonstrated by siRNA-mediated silencing approaches 7. Recent genetic studies have identified ultra-rare DCBLD2 variants associated with relapsing polychondritis, suggesting broader roles in inflammatory diseases 8.