Learning-related potentiation of synaptic strength at Cornu ammonis subfield 1 (CA1) hippocampal excitatory synapses is dependent on neuronal activity and the activation of glutamate receptors. However, molecular mechanisms that regulate and fine-tune the expression of long-term potentiation (LTP) are not well understood. Recently it has been indicated that neurogranin (Ng), a neuron-specific, postsynaptic protein that is phosphorylated by protein kinase C, potentiates synaptic transmission in an LTP-like manner. Here, we report that a Ng mutant that is unable to be phosphorylated cannot potentiate synaptic transmission in rat CA1 hippocampal neurons and results in a submaximal expression of LTP. Our results provide the first evidence that the phosphorylation of Ng can regulate LTP expression.