{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n AOPEP encodes a zinc‐dependent aminopeptidase that appears to play an important role in the normal function and maintenance of the nervous system. Studies have shown that AOPEP is widely expressed in the developing and adult human brain, and its protein product belongs to a class of proteolytic enzymes implicated in synaptogenesis and neural homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Furthermore, loss‐of‐function variants in AOPEP have been associated with progressive forms of autosomal recessive dystonia, with some individuals also exhibiting parkinsonism. This suggests that functional AOPEP is necessary for proper motor control and that its disruption can lead to significant movement disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, investigations employing gene trap integration have revealed that AOPEP (also referred to as Aminopeptidase O) produces multiple alternatively spliced isoforms. These isoforms variably include the catalytic domain and a nucleolar localization signal, indicating that differential splicing may regulate its proteolytic activity and subcellular targeting. Such regulation might be important not only for neural maintenance but also for broader cellular functions, possibly including aspects of vascular cell biology via interactions with pathways such as the renin–angiotensin system."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Together, these findings highlight AOPEP as a critical enzyme in neural development and function whose impairment leads to dystonic movement disorders. Its complex regulation through alternative splicing further suggests that precise control of its activity is essential for maintaining proper cellular homeostasis.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Michael Zech, Kishore R Kumar, Sophie Reining, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Biallelic AOPEP Loss-of-Function Variants Cause Progressive Dystonia with Prominent Limb Involvement."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mov Disord (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/mds.28804"}], "href": "https://doi.org/10.1002/mds.28804"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34596301"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34596301"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Barbara Garavaglia, Sadeq Vallian, Luigi M Romito, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AOPEP variants as a novel cause of recessive dystonia: Generalized dystonia and dystonia-parkinsonism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Parkinsonism Relat Disord (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.parkreldis.2022.03.007"}], "href": "https://doi.org/10.1016/j.parkreldis.2022.03.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35306330"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35306330"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Richard Axton, Julie A Wallis, Helen Taylor, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Aminopeptidase O contains a functional nucleolar localization signal and is implicated in vascular biology."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biochem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcb.21497"}], "href": "https://doi.org/10.1002/jcb.21497"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17803194"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17803194"}]}]}]}