Protein phosphorylation and dephosphorylation are essential to all aspects of biology.Protein phosphatase 2A (PP2A) is an important serinelthreonine phosphatase that plays a critical role in cellular physiology including cell cycle, cell proliferation, development, and regulation of multiple signal transduction pathways.PP2A is also an important tumor suppressor protein.The PP2A core enzyme comprises a 65-kD scaffold subunit (known as A or PR65 subunit) and a 36-kD catalytic subunit (or C subunit).To gain full activity towards specific substrates, the PP2A core enzyme interacts with a variable regulatory subunit to form a heterotrimeric holoenzyme.The variable regulatory subunits consist of 4 families, with at least 16 different members.In this regard, the regulatory subunits determine the substrate specificity as well as the spatial and temporal functions of PP2A.PP2A interacts with a large number of regulatory proteins and is subject to two primary forms of regulation: methylation and phosphorylation.In this presentation, I will discuss structural insights into the function of PP2A by focusing on several recent structures: the core enzyme, two holoenzymne complexes, the core enzyme bound to a PP2A-specific methyl esterase, and the phosphotyrosyl phosphatase activator (PTPA).An emphasis is given to the underlying mechanisms of PP2A function.