The intracellular mediators cyclic AMP, calcium and pH regulate sperm function through changes in protein phosphorylation. Protein phosphorylation is the net result of the actions of protein kinases and phosphatases. The protein phosphatase isoform, PPlgamma2, with a unique C-terminus extension is highly enriched in spermatozoa and testis. Changes in PPlgamma2 catalytic activity, its phosphorylation, and binding to its regulatory proteins change during epididymal maturation. Thus PPgamma2 is a key protein in sperm motility regulation; decreased enzyme activity is associated with increased motility. This review summarizes the current knowledge of this sperm protein phosphatase. The biochemical properties of its regulatory proteins, sds22 and protein 14-3-3, among others, are discussed. Future studies will elucidate sperm signalling pathways involving PP1gamma2 and determine if the unique structure of PP1gamma2 is critical to normal male gamete development and function. Understanding the role of PP1gamma2 will not only contribute to the basic understanding of male gamete functions but also has practical applications in clinical andrology and in the development of male contraceptives.