Background:The mental retardation p21-activated kinase (PAK3) protein regulates synaptic plasticity through the regulation of cytoskeleton dynamics of dendritic spines. Results: PAK3 binds the Grb4/Nck2 adaptor in brain, and inhibition of this complex alters synaptic currents but not spine morphology. Conclusion:The PAK3-Nck2 complex regulates post-synaptic transmission independently of spine dynamics. Significance: This opens perspectives in understanding the PAK3 implication in synaptic plasticity and mental retardation.