{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSEPSECS, the enzyme formally known as O‐phosphoseryl‐tRNA:selenocysteinyl‐tRNA synthase, catalyzes the ultimate step of the selenocysteine biosynthesis pathway—the conversion of a phosphoserine residue attached to tRNA(Sec) into selenocysteine via a pyridoxal phosphate–dependent reaction. Detailed biochemical and structural studies have provided critical insights into this unique reaction and have also revealed that the human enzyme (which is immunologically identical to the autoantigen SLA/LP/tRNP[Ser]Sec) plays a role in mediating autoimmune responses in conditions such as autoimmune hepatitis."}, {"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": "\nGenetic alterations in SEPSECS have been linked to profound neurodegenerative phenotypes. Mutations in this gene are associated with autosomal‐recessive progressive cerebellocerebral atrophy and pontocerebellar hypoplasia, reflecting the enzyme’s critical role in selenoprotein production and cellular antioxidative defense. In addition, common single nucleotide polymorphisms in SEPSECS have been connected with variations in serum selenium levels and risks for inflammatory disorders, while studies in human trophoblast cells suggest that changes in SEPSECS activity may also affect cell proliferation and hormone secretion. Advanced structural analyses demonstrate that SEPSECS functions as a tetramer capable of binding one or two tRNA(Sec) molecules; in pathogenic contexts, mutations often compromise protein stability and promote misfolding."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBroader genetic and epigenetic investigations have further underscored the vital importance of SEPSECS in human health. Comprehensive reviews and clinical reports have detailed that compound heterozygous mutations in SEPSECS underlie a spectrum of neurodegenerative syndromes, while recent metabolomic and epigenomic analyses have identified altered methylation of SEPSECS CpG sites in neurodegenerative disorders such as Huntington’s disease. These findings emphasize that any dysregulation of SEPSECS not only impacts selenoprotein biosynthesis but also carries far‐reaching consequences for cellular redox homeostasis and neurological development."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sotiria Palioura, R Lynn Sherrer, Thomas A Steitz, et al. 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