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In this study, we demonstrate that Pla2g4e expression peaks during early postnatal brain development, coinciding with the rapid formation of synapses. Loss-of-function experiments in primary neuronal cultures revealed that Pla2g4e expression is essential for proper dendritic development and neuronal maturation. In constitutive Pla2g4e knockout mice, we observed significant disruptions in the developmental profiles of cortical synaptic plasticity markers, accompanied by impairments in memory-related behaviors. Notably, the adeno-associated virus\u2013mediated overexpression of\n                    <jats:italic>PLA2G4E<\/jats:italic>\n                    rescued memory deficits, highlighting its functional relevance in cognitive processes. Furthermore, selective deletion of\n                    <jats:italic>Pla2g4e<\/jats:italic>\n                    in excitatory neurons of the adult brain resulted in moderate memory impairments in aged animals, suggesting an ongoing role in synaptic maintenance. Together, these findings establish PLA2G4E as a key regulator of dendritic architecture, synaptic function, and cognitive performance, and highlight its potential as a gene therapy target for neurodegenerative diseases characterized by synaptic dysfunction.\n                  <\/jats:p>","DOI":"10.26508\/lsa.202503323","type":"journal-article","created":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T20:35:56Z","timestamp":1752093356000},"page":"e202503323","update-policy":"https:\/\/doi.org\/10.26508\/lsa.crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Loss of PLA2G4E compromises synaptic structure and cognitive outcomes in mice"],"prefix":"10.26508","volume":"8","author":[{"given":"Sara","family":"Badesso","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02rxc7m23","id-type":"ROR","asserted-by":"publisher"}],"name":"Gene Therapy for CNS Disorders Program, Center for Applied Medical Research (CIMA), Instituto de Investigaci\u00f3n 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