{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPANX3 is a member of the pannexin family of channel‐forming glycoproteins that operate as single membrane channels, distinct from classical gap junction proteins. Studies have shown that, like its paralog PANX1, PANX3 is glycosylated and follows a COPII‐dependent secretory pathway for trafficking to the cell surface. In multiple tissues such as skin and cartilage, PANX3 displays unique localization patterns—ranging from clustered cell surface accumulations to diffuse intracellular distributions—indicating specialized roles in cellular physiology. These molecular features and trafficking dynamics highlight its divergence from connexins and underscore its emerging significance in intercellular signaling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn developmental contexts, PANX3 plays critical roles in regulating the balance between cell proliferation and differentiation. In cartilage, for instance, PANX3 promotes the switch of chondrocytes from a proliferative state to one favoring differentiation, likely through its function as a hemichannel that facilitates extracellular ATP release and modulates intracellular cAMP levels. In skeletal muscle, differential expression of PANX3 isoforms has been linked to both the induction of myoblast differentiation and the suppression of proliferation, suggesting that PANX3 is a pivotal regulator in myogenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond developmental regulation, PANX3 contributes to osteogenic processes and modulates inflammatory responses in various tissues. In dental and bone-related cells, PANX3 expression is associated with osteogenic differentiation—for example, by enhancing osteoblast marker expression in dental pulp–derived mesenchymal stromal cells and odontoblast-like cells—and it appears to exert an anti-inflammatory effect under conditions of immune challenge. Its dysregulation has also been observed in pathological settings, such as in osteosarcomatous transformation of sweat gland carcinomas and in patients with chronic back pain linked to intervertebral disk disorders. In addition, expression studies in pluripotent stem cells and investigations into neuropsychiatric conditions indicate that while PANX3 is broadly expressed, its functional impact is most evident in tissues undergoing differentiation and repair rather than in central nervous system disorders."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Silvia Penuela, Ruchi Bhalla, Xiang-Qun Gong, et al. 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