Protein phosphatase 2C (PP2C) was first defined as magnesium (or manganese)-dependent Ser/Thr-specific dephosphorylation activity in mammalian tissue extract (Cohen 1989). This activity was also found to be resistant to okadaic acid, a potent inhibitor of Ser/Thr-phosphatases. Because of its cation dependency, PP2C is sometimes referred as PPM (protein phosphatase, magnesium or manganese dependent). Genes encoding PP2C were subsequently isolated from yeast to humans, revealing a conserved protein phosphatase family with no apparent sequence similarity to the other Ser/Thr-phosphatases such as PP1, PP2A, and PP2B. It is also notable that eukaryotic species have more genes encoding for PP2C than those for the other Ser/Thr-phosphatase families. For example, the budding yeast Saccharomyces cerevisiae and the fission yeast Schizosaccharomyces pombe, have seven and six PP2C...