We describe here an LTP-induced gene, LIRF, which encodes a novel protein with RING finger and B30.2 domains in its N- and C-terminal portions, respectively. Each domain is encoded by one exon, suggesting that the organization of the gene was generated by exon shuffling. The amino acid sequences of the mouse, rat, and human LIRF proteins are highly conserved and contain a putative PEST sequence. LIRF is an immediate-early gene in hippocampal granule cells, and its expression is upregulated immediately after the induction of long-lasting long-term potentiation at perforant pathway-dentate gyrus synapses and returns to the basal level within 150 min. A heterologously expressed LIRF protein fused to EGFP localizes specifically to the cytoplasm in COS-7 cells. These findings suggest a possible involvement of LIRF in a limited, early phase of synaptic plasticity.