{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nConnexin45, encoded by the gene GJC1, is a versatile gap junction protein that underpins direct intercellular communication in a wide range of tissues. Its expression contributes to both homotypic and heterotypic channel formation in systems as diverse as the heart, retina, kidney and even in stem cell populations, where connexin45‐mediated coupling supports metabolic and ionic exchange. During development and in adult tissues, connexin45 is dynamically regulated and colocalizes at sites of cell–cell contact, facilitating electrical synchronization and coordinated tissue function."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the molecular level, connexin45 function is finely tuned by its interactions with key regulatory proteins and by post‐translational modifications. Its binding to scaffolding molecules such as zonula occludens‐1 (ZO‑1) helps determine its membrane localization and integration into lipid raft domains, while direct binding to calmodulin in a Ca²⁺‑dependent manner modulates channel gating. Furthermore, alterations in its promoter methylation status—as observed in colorectal and liver cancers—underscore an epigenetic mechanism that can silence GJC1 expression and impact gap junctional communication. In addition, electrophysiological studies have revealed that connexin45 exhibits rapid, asymmetric voltage‐dependent gating and temperature‐sensitive kinetics that contribute to modulation of intercellular coupling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "14"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its fundamental roles in maintaining tissue homeostasis, connexin45 influences cellular excitability and proliferation in both physiological and pathological settings. In the cardiac conduction system, for example, its presence in sinoatrial and atrioventricular regions is critical for regulating impulse propagation and ensuring proper rhythmicity; computational models have demonstrated how its rapid gating kinetics can modulate conduction delays and prevent arrhythmogenic events. Moreover, connexin45 has been implicated in cancer biology and stem cell reprogramming, where altered expression correlates with changes in cell cycle regulation and enhanced intercellular coupling. These multifaceted roles highlight GJC1 as a pivotal modulator of gap junction function with potential therapeutic implications in arrhythmia, cancer and regenerative medicine."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "21"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "R A Kaba, S R Coppen, E Dupont, et al. 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