{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n DSEL has been implicated in several, apparently diverse, biological processes. In one well‐characterized role, DSEL (dermatan sulfate epimerase–like) functions as an enzyme involved in extracellular matrix remodeling through the biosynthesis of dermatan sulfate. By catalyzing the conversion of D‐glucuronic acid to L‐iduronic acid in chondroitin/dermatan sulfate chains, DSEL contributes to the structural diversity of proteoglycans that modulate cell–matrix interactions, tissue development, and the maintenance of normal connective tissue architecture. Alterations in this pathway have been linked to connective tissue disorders such as musculocontractural Ehlers–Danlos syndrome and may also contribute to other developmental and psychiatric manifestations."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In another context, “DSEL” designates a mutant form of the parathyroid hormone (PTH)/PTH‐related peptide receptor that retains normal adenylyl cyclase activation while failing to stimulate phospholipase C (PLC). Studies employing this receptor mutant have shown that loss of the PLC arm of PTH receptor signaling alters chondrocyte differentiation and delays endochondral ossification, thereby underscoring the importance of PLC‐mediated pathways in skeletal and mineral homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, genetic studies have implicated variants in the vicinity of DSEL in multiple complex traits and diseases. For example, linkage and association analyses have identified signals near DSEL in cohorts for major depressive disorder, diaphragmatic hernia, and type 2 diabetes, as well as in prognostic models for bladder cancer; similar alterations have been observed in livestock where polymorphisms near DSEL are associated with differences in muscle lipid composition and meat quality."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, bioanalytical studies have detected the presence of a peptide fragment corresponding to “DSEL” in plasma following the oral administration of β‐conglycinin, suggesting that DSEL‐derived oligopeptides may be generated during digestion and enter the circulation, where they might have bioactive roles."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, the collective findings support a multifaceted role for DSEL. As an epimerase, it is central to dermatan sulfate biosynthesis and extracellular matrix function, while its mutated form in PTH receptor signaling models has provided key insights into the importance of PLC‐dependent pathways in skeletal development. Moreover, nearby genetic variants and derived peptides point to additional roles in disease susceptibility and nutritional biochemistry.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Thomas Müller, Shuji Mizumoto, Indrajit Suresh, et al. 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