We report the cDNA sequence of human Fe65L2. The human Fe65L2 encoded 486 amino acids; the deduced amino acid sequence was shorter by 18 amino acids than the rat protein and had 86% identity to the rat protein Three protein-protein interaction domains, a WW and two PID/PTB elements, were conserved among the Fe65 protein family. Human Fe65L2 mRNA was expressed in various tissues; a transcript of about 2.2 kb was mainly expressed in the brain. A splicing variant lacking two amino acids in the first PID/PTB element was detected. We also confirmed that the carboxyl-terminal region of PID/PTB of the Fe65L2 interacted with the intracellular domain of the Alzheimer's beta-amyloid precursor protein (APP) and APP-like proteins.