{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPodocalyxin (PODXL) is a heavily glycosylated, transmembrane sialomucin that plays a critical role in stem and progenitor cell biology. It is expressed by undifferentiated human embryonic stem cells and embryonal carcinoma cells—often carrying stem‐cell antigens—and serves as a potent marker for pluripotency. In multipotent mesenchymal stem cells, high PODXL expression defines an early progenitor population with increased clonogenicity and differentiation efficiency, while its glycan features allow for specific lectin binding that distinguishes undifferentiated cells. Collectively, these findings have provided the rationale for targeting PODXL to eliminate residual undifferentiated cells in regenerative applications."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of cancer, aberrant PODXL overexpression has been linked to an aggressive tumor phenotype across a broad spectrum of malignancies—including breast, prostate, colorectal, ovarian, bladder, pancreatic, and brain cancers. Its anti‐adhesive properties lead to diminished cell–cell junctions and enhanced migratory and invasive behaviors. Mechanistically, PODXL interacts with cytoskeletal and signaling mediators such as ezrin, gelsolin, and dynamin‐2, thereby modulating pathways (e.g. MAPK, PI3K, Rac1/Cdc42) that bolster invadopodia formation, extravasation, and metastatic spread. Moreover, PODXL expression can be regulated by several microRNAs (including miR‑199a, miR‑199b, miR‑5100, and miR‑509‑3‑5p), further underscoring its role in tumor progression and its promise as a prognostic biomarker that correlates with poor clinical outcomes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "31"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its roles in cell identity and tumor progression, PODXL is indispensable for the proper function of renal podocytes. By modulating cell–matrix interactions and maintaining a negatively charged, anti‐adhesive surface necessary for the integrity of the glomerular filtration barrier, PODXL ensures normal kidney morphogenesis and function. Its shedding into the urine makes it a promising noninvasive biomarker for podocyte injury in diverse glomerular pathologies such as diabetic nephropathy, IgA nephropathy, and obesity‐related glomerulopathy."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "32", "end_ref": "36"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Aruna Somasiri, Julie S Nielsen, Nikita Makretsov, et al. 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