{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nATP11A and ATP11C are plasma membrane flippases that continuously maintain phospholipid asymmetry by rapidly transporting phosphatidylserine (PtdSer) from the outer to inner leaflet. In precursor B cells, this activity is crucial to prevent persistent PtdSer exposure that would otherwise mark the cells for engulfment by macrophages, while complementary flippases acting through endocytic recycling further contribute to re‐establishing membrane asymmetry."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMutations in ATP11A can alter its substrate specificity such that it aberrantly flips phosphatidylcholine, disturbing the native phospholipid distribution and leading to significant developmental and neurological defects. In parallel, markedly increased expression of ATP11A has been associated with resistance of malignant lymphoblasts to small‐molecule inhibitors, indicating that abnormal levels or activity of this flippase can also influence cellular response to pharmacologic agents."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn specialized tissues, compromised ATP11A function produces distinct phenotypes: partial deletion results in loss of its phospholipid translocation activity leading to auditory synaptopathy/neuropathy, while genetic ablation in the placenta disrupts the formation and fusion of trophoblasts necessary for establishing the labyrinthine layer. These diverse findings underscore that proper ATP11A-mediated lipid flipping is essential for normal cell survival, tissue development, and the maintenance of cellular signaling integrity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Katsumori Segawa, Yuichi Yanagihashi, Kyoko Yamada, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "A sublethal ATP11A mutation associated with neurological deterioration causes aberrant phosphatidylcholine flipping in plasma membranes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI148005"}], "href": "https://doi.org/10.1172/JCI148005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34403372"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34403372"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Bin Zhang, John Groffen, Nora Heisterkamp "}, {"type": "b", "children": [{"type": "t", "text": "Resistance to farnesyltransferase inhibitors in Bcr/Abl-positive lymphoblastic leukemia by increased expression of a novel ABC transporter homolog ATP11a."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2004-09-3655"}], "href": "https://doi.org/10.1182/blood-2004-09-3655"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15860663"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15860663"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yuki Ochiai, Chigure Suzuki, Katsumori Segawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inefficient development of syncytiotrophoblasts in the "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "Atp11a"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": "-deficient mouse placenta."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.2200582119"}], "href": "https://doi.org/10.1073/pnas.2200582119"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35476530"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35476530"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Shashank Chepurwar, Sarah M von Loh, Daniela C Wigger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A mutation in ATP11A causes autosomal-dominant auditory neuropathy type 2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddac267"}], "href": "https://doi.org/10.1093/hmg/ddac267"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36300302"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36300302"}]}]}]}