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Dysfunction in dopaminergic neurotransmission within the <jats:italic>striatum<\/jats:italic> leads to movement impairments, gaiting defects, and hypo\u2010locomotion. Due to their high polarity and extreme axonal arborization, neurons depend on molecular motor proteins and microtubule\u2010based transport for their normal function. Transport defects have been associated with neurodegeneration since axonopathies, axonal clogging, microtubule destabilization, and lower motor proteins levels were described in the brain of patients with Parkinson's Disease and other neurodegenerative disorders. However, the contribution of specific motor proteins to the regulation of the nigrostriatal network remains unclear. Here, we generated different conditional knockout mice for the kinesin heavy chain 5B subunit (Kif5b) of Kinesin\u20101 to unravel its contribution to locomotion. Interestingly, mice with neuronal <jats:italic>Kif5b<\/jats:italic> deletion showed hypo\u2010locomotion, movement initiation deficits, and coordination impairments. High pressure liquid chromatography determined that dopamine (<jats:styled-content style=\"fixed-case\">DA<\/jats:styled-content>) metabolism is impaired in neuronal <jats:italic>Kif5b<\/jats:italic>\u2010<jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content>, while no dopaminergic cell loss was observed. However, the deletion of <jats:italic>Kif5b<\/jats:italic> only in dopaminergic neurons is not sufficient to induce locomotor defects. Noteworthy, pharmacological stimulation of <jats:styled-content style=\"fixed-case\">DA<\/jats:styled-content> release together with agonist or antagonist of <jats:styled-content style=\"fixed-case\">DA<\/jats:styled-content> receptors revealed selective D2\u2010dependent movement initiation defects in neuronal <jats:italic>Kif5b<\/jats:italic>\u2010<jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content>. Finally, subcellular fractionation from <jats:italic>striatum<\/jats:italic> showed that <jats:italic>Kif5b<\/jats:italic> deletion reduced the amount of dopamine D2 receptor in synaptic plasma membranes. Together, these results revealed an important role for Kif5b in the modulation of the striatal network that is relevant to the overall locomotor response.<\/jats:p><\/jats:sec><jats:sec><jats:title>Open science badges<\/jats:title><jats:p><jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/jnc14665-gra-0001.png\" xlink:title=\"image\"\/><\/jats:p><jats:p>This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/cos.io\/our-services\/open-science-badges\/\">https:\/\/cos.io\/our-services\/open-science-badges\/<\/jats:ext-link>.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc14665-fig-0008-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.14665","type":"journal-article","created":{"date-parts":[[2019,1,21]],"date-time":"2019-01-21T14:11:21Z","timestamp":1548079881000},"page":"362-380","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Neuronal <i><scp>KIF<\/scp>5b<\/i> deletion induces <i>striatum<\/i>\u2010dependent locomotor impairments and defects in membrane presentation of dopamine D2 receptors"],"prefix":"10.1111","volume":"149","author":[{"given":"Lucas E.","family":"Cromberg","sequence":"first","affiliation":[{"name":"Instituto de Biolog\u00eda Celular y Neurociencias IBCN (CONICET\u2010UBA) Facultad de Medicina Universidad de Buenos Aires Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trinidad M. 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