( Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Institute of Materia Medica,
Shanghai Institutes for Biological Sciences, the Chinese Academy of Sciences, Shanghai 200031, China)

Abstract Protein phosphatase 2A (PP2A) is a major kind of serine/threonine protein phosphatase in eukaryotic cells. PP2A has many subunits and isozymes encoded by different genes to form many different PP2A holoenzymes. PP2A plays important roles in regulation of cell cycle, signal transduction, cell differentiation, and transformation. Its activity is related to several diseases, including neurodegenerative diseases and cancer. The regulation of PP2A activity is accomplished by its subunits' expression, cellular localization, phosphorylation and methylation. The second messenger, ceramide, also plays an important role in the regulation of PP2A activity, as well as a plenty of low molecular mass inhibitors of PP2A and other protein phosphatases.