{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSynaptopodin (SYNPO) is a proline‐rich, actin‐associated protein that plays multifaceted roles in regulating cytoskeletal dynamics in a variety of cell types. In kidney podocytes, SYNPO stabilizes the actin cytoskeleton by modulating RhoA signaling—preventing its degradation through interference with Smurf1‐mediated ubiquitination—which promotes stress fiber formation and proper cell migration. In these cells, SYNPO interacts with several partners including alpha‐actinin and MAGI-1 to facilitate actin bundling and maintain the integrity of the filtration barrier, while alterations in its expression have been linked to glomerular diseases such as focal segmental glomerulosclerosis and diabetic nephropathy."}, {"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 the central nervous system, SYNPO is a critical determinant of dendritic spine architecture. It accumulates in the spine neck and is essential for the formation of the spine apparatus, where its interactions with F‐actin and alpha‐actinin modulate synaptic plasticity through local calcium signaling via ryanodine and inositol‐triphosphate receptors. Reduced expression or genetic variation of SYNPO has been implicated in neuropsychiatric disorders, including schizophrenia and Lewy body dementias, suggesting that it plays an important role in fine-tuning synaptic strength and cognitive function."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond neurons and podocytes, SYNPO expression is dynamically regulated in other tissues. In intestinal epithelial cells, butyrate uniquely induces SYNPO expression through mechanisms that may involve histone deacetylase inhibition, thereby strengthening tight junctions and promoting wound healing. Moreover, aberrant SYNPO expression—as observed in urinary sediments or in response to mechanical stimuli such as laminar shear stress in endothelial cells—has been correlated with tissue injury and impaired repair, underscoring its potential as a biomarker and therapeutic target in diverse disease states. Mutational studies and promoter analyses further implicate dysregulation of SYNPO in the pathogenesis of proteinuric disorders (including preeclampsia and FSGS) and reveal that its structural interactions, such as the “fuzzy” binding with WW-domain proteins, help fine-tune its role in actin dynamics and receptor trafficking."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "19"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Katsuhiko Asanuma, Etsuko Yanagida-Asanuma, Christian Faul, et al. 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