CatSper channels are named after the first putative cation channel of sperm. CatSper4 contains a single ion transport domain comprised of 6 transmembrane spanning regions, where the fourth transmembrane region resembles a voltage sensor and a pore forming region lies between transmembrane regions 5 and 6. The pore contains the consensus sequence T×D×W indicative of a probable Ca2+ selective channel. The four CatSper proteins are primarily localized to the plasma membrane of the distal portion of the sperm tail and presumably form a heterotetrameric, pH- and voltage-dependent Ca2+-permeable channel. nCatSper 4 is highly expressed in testis and expressed at low levels in placenta and lung.nMale mice deficient in any of the four CatSper are completely sterile but exhibit no other apparent abnormality. The major phenotypes of the null sperm are a lack of hyperactivated motility, a gradual loss of motility after isolation, and an inability to penetrate zona-intact eggs.