Genetic disruption of either the catalytic subunit (PPP3CC) or the regulatory subunit (PPP3R2) of sperm-specific calcineurin or short-term in vivo pharmacological inhibition with calcineurin inhibitors (cyclosporine A or FK506) leads to complete male infertility, with reduced sperm motility owing to an inflexible midpiece during sperm maturation in the epididymis.168 Importantly, inhibitors of sperm-specific calcineurin could act on male fertility both effectively and reversibly because inhibition of PPP3CC/PPP3R2 targets spermatozoa in the epididymis. The gene discussed is PPP3CC; the disease is male infertility.