Calcineurin (also known as protein phosphatase 3) is one of the serine/threonine phosphatase that is controlled directly by Ca²⁺ and calmodulin. The functions of calcineurin have been studied most extensively in T lymphocytes, where calcineurin transduces immunogenic signals in response to T cell receptor activation, but we are interested in the function of calcineurin in testis. It has been thought that calcineurin is related to spermiogenesis, and later, to the regulation of flagellar motility, because expression of calcineurin fluctuates during the cycle of spermatogenesis, peaking after meiosis. However, any definite physiological functions of calcineurin in testis are not elucidated.
In recent years, a growing numbers of calcineurin-binding proteins have been discovered from various tissues, most of which can inhibit the phosphatase activity of calcineurin. These proteins seem to function as tissue specific regulator for calcineurin. We found a gonad specific calcineurin-binding protein, CaNBP75. This protein also bound a small G protein, Ran. CaNBP75 may function as a mediator for crosstalk between signaling pathways of Ca²⁺ regulation and the small G protein mediated regulation in spermatogenesis, and functional analyses of CaNBP75 help to understand the physiological function of calcineurin in testis.