{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPACSIN2 is a member of the BAR‐domain protein family that plays a central role in membrane remodeling. Its F‐BAR domain facilitates membrane curvature and the generation of diverse tubules and microspikes, which are critical for the formation and stabilization of caveolae. Structural studies have revealed that PACSIN2 can drive both tubule formation and constriction through unique mechanisms—including autoinhibition in its full‐length form, regulation by PKC‐mediated phosphorylation (notably at serine 313), and essential tip‐to‐tip interactions that enhance its membrane‐deforming activity. These properties enable PACSIN2 to sculpt plasma membranes and support endocytic fission events with the recruitment of dynamin."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its membrane‐remodeling capabilities, PACSIN2 is intricately involved in intracellular trafficking, cytoskeletal dynamics, and adhesion. It participates in Golgi vesicle formation by complexing with dynamin, contributes to centrosome function and microtubule nucleation, and modulates cell migration through interactions with Rac1 and Cyclin D1. PACSIN2 also regulates endocytic recycling pathways by forming complexes with proteins such as MICAL‐L1 and EHD regulators, thereby influencing the trafficking of receptors including the epidermal growth factor receptor. Moreover, at cell–cell junctions, PACSIN2 governs the endocytosis of key adhesion molecules like VE‐cadherin and N‐cadherin, which is essential for maintaining endothelial barrier integrity and coordinating collective cell migration."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "16"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nPACSIN2 also emerges as a multifaceted player in disease pathogenesis and therapeutic responses. In hematological malignancies and inflammatory conditions, genetic polymorphisms in PACSIN2 have been linked to altered thiopurine S‐methyltransferase activity and increased sensitivity to mercaptopurine toxicity, thereby impacting treatment outcomes in acute lymphoblastic leukemia and inflammatory bowel disease. In kidney epithelial cells, PACSIN2 interacts with polycystin‐1 to modulate actin dynamics and directional migration, a process pertinent to polycystic kidney disease. The protein is additionally exploited by pathogens: it facilitates the uptake of Clostridium difficile TcdA, supports cell‐to‐cell spread of Listeria monocytogenes, and promotes hepatitis C virus assembly through its interplay with viral nonstructural proteins and modulation of lipid droplet formation. Finally, in chronic myeloid leukemia, PACSIN2 participates in a competitive protein interaction network with Cobll1 and SH3BP1 that influences Rac1 signaling and contributes to tyrosine kinase inhibitor resistance. Recent evidence also implicates PACSIN2 in the regulation of autophagy, further underscoring its impact on drug sensitivity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "25"}]}, {"type": "t", "text": ""}]}]}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Qi Wang, Marcos V A S Navarro, Gary Peng, et al. 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