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We find that the presynaptic release of the tyrosine-directed ectokinase, vertebrate lonesome kinase (VLK\/\n                    <jats:italic toggle=\"yes\">Pkdcc<\/jats:italic>\n                    ), is necessary and sufficient for the direct extracellular interaction between EphB2 and GluN1 at synapses for phosphorylation of the ectodomain of EphB2 and mediation of injury-induced pain.\n                    <jats:italic toggle=\"yes\">Pkdcc<\/jats:italic>\n                    is an essential gene in the nervous system, and VLK is enriched at synapses and released from neurons in an activity- and soluble\n                    <jats:italic toggle=\"yes\">N<\/jats:italic>\n                    -ethylmaleimide-sensitive factor activating protein receptor (SNARE)\u2013dependent manner to drive extracellular interactions. Our results show that presynaptic sensory neuron\u2013specific VLK knockout attenuates postsurgical pain in mice without changing sensorimotor performance, suggesting that VLK critically regulates synaptic protein-protein interactions and acute pain in response to injury.\n                  <\/jats:p>","DOI":"10.1126\/science.adp1007","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T19:02:32Z","timestamp":1763665352000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":5,"title":["The synaptic ectokinase VLK triggers the EphB2\u2013NMDAR interaction to drive injury-induced pain"],"prefix":"10.1126","volume":"390","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4369-667X","authenticated-orcid":true,"given":"Kolluru D.","family":"Srikanth","sequence":"first","affiliation":[{"name":"Tulane Brain Institute, Department of Cell and Molecular Biology, Tulane University, New Orleans, LA, 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