{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMultiple independent genome‐wide association studies have implicated PHLDB1 in glioma susceptibility. A recurrent single–nucleotide polymorphism (rs498872) in the regulatory region near the 5′ end of PHLDB1 has been consistently associated with an increased risk of glioma across diverse populations, including Europeans and Asians. These findings, derived from large-scale meta‐analyses and case–control investigations, underscore the contribution of common low–penetrance alleles at the 11q23.3 locus to glioma etiology."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its genetic association with glioma risk, PHLDB1 encodes the LL5α protein, a key member of the LL5 family that links extracellular signaling to cytoskeletal dynamics. LL5α, together with its homolog LL5β (encoded by PHLDB2), localizes at the basal cell cortex where it interacts—directly or indirectly—with laminin–integrin complexes to capture EB1/CLIP‐associated microtubule plus ends. This mechanistic role is critical for maintaining microtubule density, regulating adhesion turnover, and stabilizing the protrusive activity necessary for tumor cell migration and invasion. Functional studies have thus established that alterations in PHLDB1 expression or regulation may impact cell motility and invasive behavior, contributing to tumor progression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond glioma, emerging evidence suggests that genetic variants in PHLDB1 may have broader implications for disease susceptibility. Variants in or near the PHLDB1 locus have been implicated in systemic lupus erythematosus, as well as in the susceptibility to other tumor types such as pituitary adenoma. These observations indicate that PHLDB1‐related regulatory mechanisms might influence diverse cellular processes and contribute to the complex etiology of multiple human diseases."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sanjay Shete, Fay J Hosking, Lindsay B Robertson, et al. 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