Consistent with an essential role of hyperactivation for fertilization competency, low motility and/or defects in hyperactivation is one of the most common phenotypes observed in sperm from many different infertile knock-out models, including those used in the present work (i.e., Catsper−/−, Adcy10−/−, Slo3−/− and Pmca4−/−)18, 21, 24, 32. The gene discussed is ATP2B4; the disease is Infertility.