Background AMPA receptor mediates the most excitatory synaptic transmission in the central nervous system, and is involved in the pain signal transmission. As a member of trans-membrane AMPA receptor regulated protein family, Stargazin serves as a critical protein involved in the trafficking and synaptic targeting of AMPA receptors and plays an important role in the AMPA receptor-mediated pain. Objective In this review, we will bring together the evidence that Stargazin controls the AMPA receptor subunits trafficking, synaptic insertion and regulates pain signal transmission. Content Stargazin is responsible for the AMPA receptor subunits trafficking into cellular membrane. The interaction between Stargazin and PSD-95 controls the synaptic insertion of AMPA receptor subunits. The phosphrylation of Stargazin affects the interaction with PSD-95. Therefore, Stargazin may be implicated in pain transmission via regulating AMPA receptor function. Trend Downregulation of Stargazin expression or disrupting the postsynaptic interaction between stargazin and PSD-95 may be a new approach for pain control and deserves further investigation.