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The XCL1\u2013XCR1 axis is of particular interest because XCR1 is selectively expressed on mature conventional type 1 dendritic cells (cDC1s), where it supports communication with activated CD8\n                    <jats:sup>+<\/jats:sup>\n                    \u2009T cells and NK cells and promotes antigen cross\u2010presentation. This selectivity has made XCR1 an attractive target for dendritic cell\u2013based cancer vaccines, while emerging evidence also links XCL1\u2013XCR1 signalling to neuroinflammation and pain. Despite its therapeutic potential, the mechanisms governing XCR1 activation and trafficking remain understudied. Here, we characterize XCR1 expression, membrane trafficking, and basal internalization to define mechanisms that may influence therapeutic targeting. We show that XCR1 undergoes constitutive internalization through a \u03b2\u2010arrestin\u2013independent but adaptor protein 2 (AP2)\u2013dependent pathway, distinguishing it from other chemokine receptors with constitutive endocytosis. Furthermore, we identify specific sequence motifs critical for its subcellular localization and intracellular trafficking. These findings provide new mechanistic insights into XCR1 regulation and may inform the development of targeted therapeutics and antigen\u2010delivery strategies in cancer and inflammation.\n                  <\/jats:p>","DOI":"10.1111\/bcpt.70318","type":"journal-article","created":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T04:29:01Z","timestamp":1791779341000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanisms of XCR1 Membrane Trafficking and Constitutive Endocytosis"],"prefix":"10.1111","volume":"139","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-8719-0526","authenticated-orcid":false,"given":"Qiao","family":"Li","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen 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