{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n B3GNT5 encodes the beta‐1,3‑N‑acetylglucosaminyltransferase 5 enzyme, a critical glycosyltransferase that catalyzes formation of the lactotriaosylceramide (Lc3) structure—the key precursor for lacto‐ and neolacto‐series glycosphingolipids. Its activity is essential for normal embryonic development, as loss‐of‐function in mice leads to absent lacto‐neolacto glycosphingolipids, disruptions in membrane microdomain (GEM) clustering, and altered cell adhesion and differentiation processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In cancer, dysregulation of B3GNT5 has been implicated in several tumor types. For instance, in glioblastoma, B3GNT5 is markedly elevated in glioma stem cells, where its high expression supports neurosphere formation and is associated with poorer patient overall survival, suggesting an important role in maintaining malignant stem cell properties."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Likewise, in liver cancer the long non‐coding RNA MIR4435‑2HG enhances tumor progression via a MIR4435‑2HG/miR‑136‑5p/B3GNT5 regulatory axis, further supporting a role for increased B3GNT5 activity in oncogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In contrast, studies in hypopharyngeal squamous cell carcinoma and hydatidiform moles have identified microRNAs—miR‑203 and miR‑30a, respectively—that target B3GNT5, with their downregulation of B3GNT5 contributing to increased tumor growth or altered trophoblast cell functions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Additional studies have suggested prognostic associations in breast cancer, with aberrant B3GNT5 expression correlating with patient survival, and a hub role in glycosphingolipid biosynthesis-related pathways in acute myocardial infarction has also been noted."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, although the B3GNT5 gene was once posited as a candidate for the ETEC F4ab/ac receptor in pigs, subsequent genetic analyses did not confirm this function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, B3GNT5 plays a central role in the biosynthesis of lacto‐ and neolacto‐series glycosphingolipids, contributing to membrane organization, signaling, and cell adhesion during normal development. Its aberrant regulation is implicated in the progression of diverse diseases—especially various cancers—thereby highlighting its potential as a biomarker and therapeutic target.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Franziska Biellmann, Andreas J Hülsmeier, Dapeng Zhou, et al. 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