Fast excitatory synaptic transmission in the brain is mediated by glutamate acting on postsynaptic AMPA receptors. Recent studies have revealed a substantial number of AMPA receptor auxiliary proteins, which potentially contribute to the regulation of AMPA receptor trafficking, subcellular receptor localization, and receptor gating properties. Here we examined the AMPA receptor interactomes from cortex, hippocampus, and cerebellum by comprehensive interaction proteomics. The study reveals that AMPA receptor auxiliary proteins are engaged in distinct brain region-specific AMPA receptors subcomplexes, which might underlie brain region-specific differential regulation of AMPA receptor properties. Depending on the brain region, an interacting protein can be involved in an AMPA and a non-AMPA receptor complex.