The AMPA glutamate receptor (AMPAR) is the major type of synaptic excitatory ionotropic receptor in the brain. The most abundant AMPAR subtypes in the hippocampus are GluA1/2 and GluA2/3 heterotetramers. Each subtype contributes differentially to mechanisms of synaptic plasticity, which may be in part caused by how these receptors are regulated by specific associated proteins. A broad range of AMPAR interacting proteins have been identified and several were shown to affect biogenesis, AMPAR trafficking, and channel properties, alone or in distinct assemblies, and several revealed preferred binding to specific AMPAR subunits. To date, a systematic separate interactome analysis of the major GluA1/2 and GluA2/3 AMPAR subtypes is lacking. To reveal interactors belonging to specific AMPAR sub-complexes, we performed both quantitative and interaction proteomics on hippocampi of wildtype and GluA1- or GluA3 knock-out mice. Whereas GluA1/2 receptors co-purified TARP-γ8, PRRT1 and CNIH2 with highest abundances, GluA2/3 receptors revealed strongest co-purification of CNIH2, TARP-γ2, and OLFM1. Further analysis revealed that TARP-γ8-PRRT1 can interact directly, and co-assemble into an AMPAR subcomplex especially near the synapse.