{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nXylose transferase II, encoded by the XYLT2 gene, is a key enzyme that catalyzes the first and rate‐limiting step of glycosaminoglycan biosynthesis. By transferring a single xylose moiety from UDP‐xylose to specific serine residues on proteoglycan core proteins, XT‐II initiates the formation of the common tetrasaccharide linker essential for building extracellular matrix proteoglycans. This fundamental catalytic activity underscores its importance for cellular and tissue homeostasis, as demonstrated by biochemical studies showing that soluble forms of XT‐II display properties comparable to those of the well‐characterized XT‐I isoenzyme."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMutations in XYLT2 have been linked to spondyloocular syndrome, a recessively inherited disorder characterized by features such as generalized osteoporosis, cataracts, spinal compression fractures, and sensorineural hearing loss. Clinical case studies have revealed that loss‐of‐function mutations in XYLT2 result in reduced enzyme activity and defective proteoglycan assembly in tissues including bone, eye, heart, and inner ear. In addition, the regulation of the XYLT2 promoter—mediated in part by Sp1 family binding sites—ensures its constitutive expression, while circulating serum XT activity (predominantly due to XT‐II) has emerged as a potential biomarker for proteoglycan synthesis and tissue remodeling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nStructural and cellular investigations have further delineated XT‐II’s biochemical characteristics and its indispensable role in proteoglycan homeostasis. Detailed analyses indicate that XT‐II shares similar pH, temperature, and cofactor dependencies with XT‐I but exhibits distinct features in intracellular targeting and substrate inhibition by nucleotides and glycosaminoglycans. Moreover, functional studies utilizing gene knockdown and CRISPR/Cas9‐mediated knockout approaches have demonstrated that cells lacking functional XT‐II (in combination with diminished XT‐I activity) suffer from reduced proliferation and viability, emphasizing its nonredundant role in maintaining extracellular matrix integrity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sylvia Schön, Christian Prante, Claudia Bahr, et al. 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