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Background: Schizophrenia is a highly heritable disorder with a polygenic architecture, and growing evidence points to glutamatergic dysfunction—particularly involving NMDA receptor hypofunction and impaired synaptic plasticity—as a key mechanistic contributor. The latest Psychiatric Genomics Consortium (PGC3) genome-wide association study reinforced synaptic biology as a major locus of common variant risk.Methods: Using MAGMA gene-set analysis, we examined polygenic enrichment in the PGC3 European-ancestry schizophrenia GWAS summary statistics (53,386 cases, 77,258 controls). Two hypothesis-driven glutamatergic/synaptic plasticity gene sets were tested: a narrow core set (23 genes) focused on ionotropic receptors and direct modulators, and an expanded set (130 genes) that additionally included transporters, metabolic enzymes, scaffolding proteins, and downstream plasticity cascades (BDNF-TrkB, mTOR, CREB, immediate-early genes). Monoaminergic (104 genes) and housekeeping (184 genes) sets served as negative controls. Competitive gene-set testing was performed with Bonferroni correction and false-discovery rate estimation.Results: The expanded glutamate/plasticity set showed significant enrichment for schizophrenia polygenic signal (p = 0.0033; Bonferroni-corrected p = 0.0134; FDR ≈ 0.013), with a higher mean association strength than the genome-wide average. The narrower core set displayed only a trend (p = 0.092). Neither control set was enriched (monoaminergic p = 0.186; housekeeping p = 0.152). Post-hoc exploration highlighted contributions from intracellular regulators, including mTOR pathway components, CREB targets, and immediate-early genes.Conclusions: Common risk variants in schizophrenia converge preferentially on broad glutamatergic signalling and downstream synaptic plasticity mechanisms rather than solely on surface receptors or monoaminergic pathways. These findings support the development of therapeutic strategies targeting synaptic plasticity to address persistent cognitive deficits in the disorder.