{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The CLIP1 gene product (commonly known as CLIP‐170) functions as a multifunctional microtubule plus‐end tracking (+TIP) protein that plays a central role in regulating microtubule dynamics and linking the microtubule network to diverse cellular processes. Structural and live‐cell imaging studies have demonstrated that CLIP‐170 binds transiently to the growing tips of microtubules—often in cooperation with end‐binding (EB) proteins—and acts as a “polymerization chaperone” by promoting tubulin assembly and suppressing catastrophe events."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, its interaction with key regulatory proteins is central to its function. For example, the direct binding of CLIP‐170 to the CAP‐gly domains of proteins such as p150<small>(Glued)</small> facilitates the recruitment and activation of the dynein/dynactin complex, thereby linking microtubule dynamics to motor‐driven transport."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Moreover, interactions with regulatory factors like LIS1 and IQGAP1 help to coordinate microtubule capture at the cell cortex, contributing to processes such as cell polarization and directional migration."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Recent evidence also highlights that the activity of CLIP‐170 is modulated by phosphorylation events. For instance, AMPK‐mediated phosphorylation of CLIP‐170 adjusts microtubule dynamics and supports cytoskeletal reorganization necessary for enhanced phagocytosis in immune cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In addition, when CLIP1 is involved in oncogenic fusion events—as seen in certain Spitz tumors where CLIP1–ALK fusions are detected—its normal microtubule‐binding domains provide the structural framework that may aberrantly activate kinase signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies indicate that CLIP‐170 acts as an essential hub at microtubule plus ends by integrating structural, motor, and signaling components. Its ability to transiently bind microtubule tips, recruit dynein/dynactin via CAP‐gly interactions, and respond to regulatory phosphorylation events enables it to drive processes ranging from cytoskeletal polarization and migration to phagocytosis, and even, when disrupted, to contribute to disease pathogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "6"}, {"type": "fg_f", "ref": "2"}, {"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Masaki Fukata, Takashi Watanabe, Jun Noritake, et al. 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