{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CASKIN1 is a neuronal scaffolding protein that plays a pivotal role in organizing synaptic architecture and modulating signal transduction at both pre‐ and postsynaptic sites. Its interaction with the multi‐domain adaptor CASK is mediated by a short, conserved peptide motif, which enables CASKIN1 to form alternative tripartite complexes (with CASK and Velis) that couple to the cytoplasmic tail of neurexin, thereby influencing synaptic adhesion and neurotransmission."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Structurally, CASKIN1 comprises multiple ankyrin repeats, an atypical Src homology 3 (SH3) domain, and tandem sterile alpha motif (SAM) domains; the SAM modules can self‐assemble into helical polymers that likely contribute to the physical organization of the active zone and the clustering of synaptic components."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": " Functional in vivo studies reveal that loss of CASKIN1 results in notable behavioral alterations—including changes in gait, enhanced pain sensitivity, anxiety‐like behavior, and deficits in memory and spatial learning—underscoring its essential contribution to synaptic plasticity and dendritic spine maintenance, potentially through interactions with other postsynaptic scaffold proteins such as Shank2 and modulation of AMPA receptor localization."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Moreover, the atypical SH3 domain of CASKIN1 selectively binds lysophosphatidic acid, suggesting that it may mediate the association of CASKIN1 with membrane surfaces in response to lipid signaling cues."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}, {"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Finally, regulatory studies indicate that downregulation of CASKIN1—such as via targeting by specific microRNAs—can promote viral proliferation, hinting at broader roles in maintaining neuronal health."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Collectively, these findings position CASKIN1 as a critical hub in synaptic signaling networks, where its multifaceted protein–protein and protein–lipid interactions are essential for establishing and maintaining proper neural connectivity and function.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ryan L Stafford, Jason Ear, Mary Jane Knight, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "CASK participates in alternative tripartite complexes in which Mint 1 competes for binding with caskin 1, a novel CASK-binding protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "20026421"}], "href": "https://doi.org/20026421"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12040031"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12040031"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ryan L Stafford, Elizabeth Hinde, Mary Jane Knight, et al. 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