YWK-II protein is a sperm membrane component, structurally related to human placenta amyloid precursor protein homolog (APPH) and rat amyloid precursor-like protein 2 (APLP2). Its transmembrane-cytoplasmic domain has high homology (70.6%) with that of betaA4-amyloid precursor protein (APP) found in brain plaques of subjects with Alzheimer's disease. The gene encoding the YWK-II protein is expressed in various mammalian cells and tissues. In the present study, splicing patterns of YWK-II mRNA and the content of YWK-II mRNA in mouse testes, eggs, and cumulus cells were determined. Three different YWK-II transcripts were found in testes and eggs, while cumulus cells contained an additional transcript. In mouse eggs, the content of YWK-II transcript exceeded that of APP. An alternative splicing region was located in the vicinity of the kunitz protease inhibitor (KPI) domain, which may be the basis for the formation of multiple transcripts. YWK-II protein was immunolocated in male and female gametes. It was localized in the plasma membrane of mouse eggs and spermatozoa. In the male reproductive system of the mouse, the YWK-II gene was expressed in germ cells at various stages of differentiation. In mature spermatozoa, the YWK-II protein occurred in the plasma membrane enveloping the acrosome. Triggering the acrosome reaction incited a release of the YWK-II protein attached to the liberated membrane vesicles. The occurrence of the YWK-II protein in the plasma membranes of mouse gametes suggests its involvement in sperm-egg interaction.