{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nObscurins, giant modular proteins encoded by the OBSCN gene, are essential organizers of the striated muscle cytoskeleton. They function as molecular scaffolds that link myofibrillar components to the sarcoplasmic reticulum and sarcolemma by interacting with an array of binding partners. For example, studies show that obscurins directly bind small ankyrin‐1 (sAnk1) via specific cytoplasmic sequences to secure sarcoplasmic reticulum positioning, while other work has delineated the complete modular architecture of obscurin, which contains multiple immunoglobulin‐like domains, Rho–guanine nucleotide exchange factor (GEF) motifs and kinase domains that underlie its role in myofibril assembly. Moreover, obscurins interact with titin at Z‐discs and with myomesin at the M‐band, and can even activate Rho family GTPases (e.g. TC10) to trigger new sarcomere formation. These findings underscore the structural and signaling functions of obscurins in maintaining myofibrillar integrity and regulating contractile apparatus assembly."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of cardiac muscle, mutations in OBSCN have been implicated in cardiomyopathies. Specific aberrations—for instance, point mutations that impair binding of obscurin to titin domains or alter its sarcomeric localization—have been associated with hypertrophic cardiomyopathy and related contractile defects. These observations suggest that structural integrity provided by obscurins is critical for normal cardiac function and that even subtle alterations in its binding capabilities can predispose to arrhythmia or myopathy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond muscle, obscurins appear to have tumor‐suppressive roles in non‐muscle epithelia. In normal breast and pancreatic tissues, giant obscurins contribute to cell–cell adhesion and regulate intracellular signaling cascades, such as by binding to the regulatory subunit of PI3K. Loss of obscurins has been associated with epithelial-to-mesenchymal transition, enhanced cell survival, increased migratory and invasive behaviors, and even altered apoptotic responses. In addition, certain OBSCN polymorphisms may be linked to airway inflammatory responses. Collectively, these findings implicate obscurins in the maintenance of tissue architecture and in suppressing oncogenic transformation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Aikaterini Kontrogianni-Konstantopoulos, Ellene M Jones, Damian B Van Rossum, et al. 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