{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Ceruloplasmin (CP) is a multicopper oxidase whose principal biochemical function is to catalyze the oxidation of highly reactive ferrous iron (Fe²⁺) to the less toxic, transport‐compatible ferric form (Fe³⁺) – a reaction essential for proper iron efflux and homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In the central nervous system, CP is critical not only for iron regulation but also for coordinating copper metabolism; for instance, the copper‐transporting ATPase ATP7B delivers copper to CP in cerebellar Purkinje neurons to support its oxidase activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n CP expression is subject to tight multi‐layered regulation. At the posttranscriptional level, interferon‐γ–induced mechanisms such as the GAIT pathway control CP mRNA translation. In this process, phosphorylation‐dependent release of ribosomal protein L13a (and ancillary factors like GluProRS) enables binding to a specific GAIT element in the 3′ untranslated region of CP mRNA, thereby mediating translational silencing under inflammatory conditions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": " In parallel, CP gene transcription is enhanced by hypoxic stimuli via a HIF-1α–dependent mechanism; this links oxygen and copper sensing to CP expression and plays a role in enabling adaptive responses to altered metabolic or oxidative states."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Clinically, disrupted CP expression or activity is a hallmark in several disorders of copper and iron metabolism. For example, reduced CP levels accompany Wilson disease and certain congenital glycosylation defects, making CP both a functional mediator in metal homeostasis and a valuable diagnostic biomarker."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Suh Young Jeong, Samuel David "}, {"type": "b", "children": [{"type": "t", "text": "Glycosylphosphatidylinositol-anchored ceruloplasmin is required for iron efflux from cells in the central nervous system."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M301988200"}], "href": "https://doi.org/10.1074/jbc.M301988200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12743117"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12743117"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Natalie Barnes, Ruslan Tsivkovskii, Natalia Tsivkovskaia, et al. 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