{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Dysbindin‐related proteins—including dystrobrevin‐binding protein 1 (DTNBP1, commonly known as dysbindin) and members of the dystrobrevin family—play multifaceted roles in both muscle and brain. In skeletal muscle, these proteins are critical components of the dystrophin‐associated protein complex (DAPC) that not only provides a structural link between the cytoskeleton and extracellular matrix but also orchestrates intracellular signaling events. For example, dystrophin and its partners regulate satellite cell polarity and asymmetric division that are required for effective muscle regeneration."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, dysbindin is biochemically associated with core elements of the DAPC in muscle, acting as an adaptor whose levels are modulated in dystrophin‐deficient conditions, thereby potentially influencing membrane stability and signaling cascades."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the central nervous system, DTNBP1/dysbindin has been implicated in the regulation of presynaptic function and neurotransmitter release. A reduction of dysbindin in specific hippocampal circuits correlates with alterations in glutamatergic transmission and has been linked to cognitive deficits observed in schizophrenia."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Moreover, ubiquitin ligases such as TRIM32 regulate dysbindin turnover via ubiquitination, suggesting that post‐translational modifications of dysbindin are important for maintaining proper synaptic vesicle dynamics."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its scaffold function at the membrane, dystrobrevin itself interacts with intracellular motor proteins (e.g., kinesin heavy chains), thereby facilitating the transport and precise localization of DAPC components to specialized subcellular domains in neurons."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Furthermore, genetic variation in DTNBP1 has been associated with volumetric changes in key brain areas such as the hippocampus"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ", underscoring its importance in neurodevelopment and synaptic integrity.\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, studies converge to demonstrate that DTNBP1/dysbindin and its interacting partners serve as critical adaptors that integrate the structural and signaling functions of the DAPC. This multimodal role is essential for maintaining muscle membrane integrity, regulating satellite cell regeneration, and ensuring proper synaptic organization and neurotransmission in the brain. Disruption of these pathways may contribute to a spectrum of pathologies, including neuromuscular dystrophies and psychiatric disorders.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Nicolas A Dumont, Yu Xin Wang, Julia von Maltzahn, et al. 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