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Most synaptic proteomic studies capture endpoint snapshots following training, overlooking molecular changes occurring during learning itself. We previously established TurboID proximity proteomics as an approach to capture protein-level changes during learning in the nervous system of\n                  <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                  . Here, we apply this strategy to synapses. Trained synapses exhibited a distinct proteome compared with mock-trained controls, with pathways enriched for neurotransmission, synaptic reorganisation, protein trafficking, and autophagy. Enrichment of autophagy proteins led us to investigate the cathepsin B orthologue CPR-4, a previously uncharacterised candidate for learning identified exclusively in trained synapses. Functional validation identified CPR-4 as a novel regulator of memory: CPR-4 is required for learning, and the absence of CPR-4 results in trained synaptic proteomes that are more like those of mock-trained synapses. Our findings support a model through which CPR-4 promotes synaptic remodelling required for learning through targeted protein clearance.\n                <\/jats:p>","DOI":"10.64898\/2026.09.13.751219","type":"posted-content","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T11:40:13Z","timestamp":1789558813000},"source":"Crossref","is-referenced-by-count":0,"title":["Synaptic proteomics identifies cathepsin B as a regulator of synapse remodelling during learning"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-8498-6901","authenticated-orcid":false,"given":"Aelon","family":"Rahmani","sequence":"first","affiliation":[{"name":"College of Medicine and Public Health, Flinders Health and Medical Research Institute, Flinders University, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2653-3078","authenticated-orcid":false,"given":"Michaela 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