The structure of synaptophysin, an integral membrane protein present in synaptic vesicles, is highly conserved. We report the sequence analysis of a clone, HL-5, isolated from a human erythroleukemia cell cDNA library, that is similar to synaptophysin in DNA and amino acid sequence. The predicted protein product derived from this clone is truncated, and the tissue distribution of HL-5 is different from that of synaptophysin. Thus, HL-5 appears to be a member of a previously undescribed family of synaptophysin-like genes.