{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nDisabled‐2 (Dab2) is a multifunctional adaptor protein that orchestrates clathrin‐mediated endocytosis by binding specific receptor motifs, phosphoinositides, clathrin and other coat components to couple cargo selection with vesicle assembly. In many cell types, Dab2 associates with receptors such as the low‐density lipoprotein family (e.g., megalin), integrins and TGF‑β receptors – ensuring their proper internalization and recycling – and thereby maintains epithelial polarity and proper receptor trafficking. This endocytic function is underscored by studies showing that Dab2 recruitment to clathrin‐coated pits is essential for efficient uptake of ligands like transferrin, lipoproteins and albumin, and that disruption of Dab2 impairs endocytic vesicle formation and receptor localization at the plasma membrane."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in endocytosis, Dab2 functions as a critical modulator of intracellular signaling pathways that determine cell fate and tissue organization. It participates in TGF‑β–triggered epithelial–mesenchymal transition (EMT), where it regulates integrin activation and cell survival, and modulates both Ras/MAPK and Wnt/β‑catenin signal transduction by stabilizing key components such as Axin. Dab2’s regulatory input has been implicated in visceral endoderm formation during early embryogenesis, in tumor suppression by dampening mitogenic signals, and in preserving epithelial integrity through coordinated receptor trafficking."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "21"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond endocytosis and signaling, Dab2 plays diverse roles in modulating cellular differentiation, immune regulation and tissue homeostasis. Its expression governs macrophage polarization and inflammatory responses while influencing adipogenic commitment in juvenile progenitors, neuronal plasticity and mammary cell turnover during involution. Moreover, Dab2 has been shown to regulate cardiac differentiation and contribute to stem cell maintenance in hair follicles, and its dysregulation is associated with inflammatory diseases, fibrosis and even tumor progression in certain contexts. These findings emphasize that Dab2 acts as a nexus by integrating endocytic trafficking with key signaling events that control cell adhesion, survival, differentiation and inflammatory signaling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "22", "end_ref": "34"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sanjay K Mishra, Peter A Keyel, Matthew J Hawryluk, et al. 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