During mammalian fertilization, Ca²⁺ signaling plays a central role in sperm capacitation and motility to the fusion between sperm and egg¹. Several Ca²⁺-permeable ion channel proteins have been characterized in mammalian sperm. However, only the four mammalian CatSper members (CatSpers 1-4) are restrictively expressed in the testis and are clearly shown to be required for male fertility².

CatSper channels are named after the first putative cation channel of sperm³. 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 channel⁴. 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 ⁵. 
CatSper 4 is highly expressed in testis and expressed at low levels in placenta and lung⁶.

Male 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 eggs⁷.