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Phosphorylation of GABAA receptors is an important mechanism for dynamically modulating inhibitory synaptic function in the mammalian brain. In particular, phosphorylation of tyrosine residues 365 and 367 (Y365/7) within the GABAA receptor γ2 subunit negatively regulates the endocytosis of GABAA receptors and enhances synaptic inhibition. Here we show that Fyn, a Src family kinase (SFK), interacts with the γ2 subunit in a phosphorylation-dependent manner. Furthermore, we demonstrate that Fyn binds within a region of the γ2 intracellular domain that is centered on residues Y365/7, with the phosphorylation of Y367 being particularly important for mediating this interaction. Tyrosine phosphorylation of the γ2 subunit is significantly reduced in the hippocampus of Fyn knockout mice, suggesting that Fyn is an important kinase that contributes to the phosphorylation of this subunit in vivo. Tyrosine phosphorylation of the γ2 subunit is not completely abolished in Fyn kinase mice, suggesting that other SFKs, such as Src, also contribute to maintaining and regulating the endogenous phosphorylation level of γ2-containing GABA(A) receptors. In summary, we demonstrate Fyn as one of the SFKs that binds to and phosphorylates the γ2 subunit of the GABAA receptor. This has important implications for the regulation of synaptic GABAA receptors via signaling pathways that lead to the activation of Fyn kinase.