{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMPDZ (also known as MUPP1) functions as a multidomain scaffolding protein that organizes and stabilizes protein complexes at epithelial cell junctions. It interacts directly with components of tight junctions—for example, by binding the cytoplasmic tail of the coxsackievirus and adenovirus receptor (CAR) and recruiting other junctional proteins—as well as with G‐protein–coupled receptors such as the human somatostatin receptor 3, thereby targeting them to tight junction subdomains. In kidney epithelial cells, MPDZ forms complexes with ion channels (e.g. Kir4.2) to regulate their cell surface localization, and it participates in multimolecular assemblies with proteins like Patj and PALS-1 to maintain cell polarity and junctional integrity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the nervous system, MPDZ is implicated in the regulation of receptor signaling and neurodevelopment. Studies have linked genetic variations in MPDZ to Mendelian forms of congenital hydrocephalus and aberrant neural plate bending during neurulation, underscoring its role in neuroepithelial cell remodeling. MPDZ also associates with receptors such as the MT₁ melatonin receptor and NMDA receptor complex proteins to modulate G-protein and glutamatergic signaling. In parallel, MPDZ dysfunction has been connected with alcohol withdrawal severity and may contribute to altered excitatory neurotransmission and auditory defects, thereby expanding its relevance to neuropsychiatric disorders."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional studies have expanded the functional landscape of MPDZ to include roles in reproductive and ocular systems as well as tumor suppression. In spermatozoa, MPDZ is localized to the acrosomal and equatorial regions, where it helps organize signaling molecules essential for the acrosome reaction and fertilization. Beyond reproduction, association studies have implicated MPDZ in keratoconus and chorioretinal anomalies, suggesting its involvement in ocular physiology. In the realm of oncology, altered MPDZ expression and methylation have been linked to lung cancer suppression and colorectal cancer progression, illustrating its potential as a diagnostic and prognostic marker."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "14", "end_ref": "21"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Carolyn B Coyne, Tauni Voelker, Susan L Pichla, et al. 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