Background: Anti-ribosomal P protein autoantibodies (anti-P) are associated with psychosis and cognitive dysfunction in patients with systemic lupus erythematosus (SLE), yet the underlying mechanisms remain undefined, hindering targeted therapies. Anti-P cross-react with a neuronal surface protein (NSPA), alter glutamatergic synaptic transmission and plasticity in hippocampal slices, and impair spatial memory in a short-term passive transfer mouse model. NSPA knockout mice display spatial memory deficit linked to reduced NMDAR activity and postsynaptic density (PSD) levels, along with an increased membrane-associated tyrosine phosphatase PTPMEG, suggesting disrupted glutamatergic receptor trafficking. Here, we investigated the acute effects of anti-P on receptor cell surface expression and trafficking in cultured hippocampal neurons and their long-term impact on hippocampal components and spatial memory in anti-P( +) immunized mice.