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While the roles of <jats:styled-content style=\"fixed-case\">APs<\/jats:styled-content> 1\u20133 are broadly established, comparatively little is known about <jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content>\u20104 and <jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content>\u20105. Current evidence suggests that <jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content>\u20104 mediates <jats:styled-content style=\"fixed-case\">TGN<\/jats:styled-content> to endosome transport of specific cargo proteins, such as the amyloid precursor protein <jats:styled-content style=\"fixed-case\">APP<\/jats:styled-content>, and that it is involved in basolateral sorting in polarized cells. Furthermore, several independent studies have reported human patients with mutations in <jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content>\u20104 genes. <jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content>\u20104 deficiency causes severe intellectual disability and progressive spastic para\u2010 or tetraplegia, supporting an important role for <jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content>\u20104 in brain function and development. The newly discovered <jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content>\u20105 complex appears to be involved in endosomal dynamics; its precise localization and function are still unclear. Intriguingly, <jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content>\u20105 deficiency is also associated with progressive spastic paraplegia, suggesting that <jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content>\u20105, like <jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content>\u20104, plays a fundamental role in neuronal development and homeostasis. The unexpected phenotypic parallels between <jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content>\u20104 and <jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content>\u20105 patients may in turn suggest a functional relationship of the two <jats:styled-content style=\"fixed-case\">APs<\/jats:styled-content> in vesicle trafficking.<\/jats:bold><\/jats:p>","DOI":"10.1111\/tra.12028","type":"journal-article","created":{"date-parts":[[2012,11,21]],"date-time":"2012-11-21T07:02:16Z","timestamp":1353481336000},"page":"153-164","source":"Crossref","is-referenced-by-count":139,"title":["Adaptor Protein Complexes <scp>AP<\/scp>\u20104 and <scp>AP<\/scp>\u20105: New Players in Endosomal Trafficking and Progressive Spastic Paraplegia"],"prefix":"10.1111","volume":"14","author":[{"given":"Jennifer","family":"Hirst","sequence":"first","affiliation":[{"name":"Cambridge Institute for Medical Research University of Cambridge  Wellcome Trust\/MRC Building Cambridge CB2 0XY 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