Tetraspanin 7 (TSPAN7) a member of the tetraspanin superfamily associates dynamically with numerous partner proteins in tetraspanin-enriched microdomains (TEMs) of the plasma membrane (Boucheix and Rubinstein, 2001). TSPAN7 promotes filopodia and dendritic spine formation in cultured hippocampal neurons, and is required for spine stability and normal synaptic transmission. Via its C-terminus, TSPAN7 interacts with the PDZ domain of protein interacting with C kinase 1 (PICK1), to regulate PICK1 and GluR2/3 association and AMPA receptor trafficking (Bassani et al. 2012). PICK1 is involved in the internalization and recycling of AMPA receptors (AMPARs) (Perez et al. 2001). In hippocampal neurons, TSPAN7 may regulate AMPA receptor trafficking by limiting PICK1 accessibility to AMPA receptors and suggest an additional mechanism for the functional maturation of glutamatergic synapses, whose impairment is implicated in intellectual disability (Bassani et al. 2012). Constitutively recycling GluR2 containing AMPA receptors in the plasma membrane are stabilized by the action of NSF ATPase activity which disassociates PICK from GluR2 thereby retaining AMPA receptors in the plasma membrane.