DAB2 (disabled homolog 2) is a multifunctional endocytic adaptor protein that serves as a clathrin-associated sorting protein essential for clathrin-mediated endocytosis of cargo proteins including LDL receptors, integrins, and CFTR 1. DAB2 functions independently of AP-2 complexes and recognizes NPXY internalization motifs, facilitating cargo recruitment to clathrin-coated pits while binding to phosphatidylinositol 4,5-bisphosphate 1. Beyond endocytosis, DAB2 regulates multiple signaling pathways: it facilitates TGF-β receptor signaling and SMAD2 phosphorylation, modulates Wnt/β-catenin signaling through β-catenin stabilization, and participates in integrin-mediated signaling via focal adhesion kinase activation 2. In albumin reabsorption within the proximal tubule, DAB2 forms a multireceptor complex with megalin and cubilin to mediate albumin uptake and lysosomal trafficking 3. Notably, DAB2 exhibits tumor-suppressive properties; its expression is frequently lost in human malignancies (74.9% of cancer tissues), often through promoter hypermethylation (34.54% of loss-expressing tissues) 4. Loss of DAB2 correlates with poor prognosis and enhanced cancer cell proliferation 5. Emerging evidence indicates DAB2's involvement in immune responses: DAB2+ tumor-associated macrophages interact with cancer-associated fibroblasts to reinforce immune barriers and promote immunotherapy resistance in hepatocellular carcinoma 6. Additionally, TRIM16-mediated K63-ubiquitination of DAB2 promotes vascular calcification through integrin β1 endocytosis and FAK-STAT3 signaling activation 2.