Protein phosphatase type 2A (PPP2R1A) is an essential protein serine/threonine phosphatase that is conserved in all eukaryotes. PPP2R1A is a key enzyme within various signal transduction pathways as it regulates fundamental cellular activities such as DNA replication, transcription, translation, metabolism, cell cycle progression, cell division, apoptosis and development. The core enzyme consists of catalytic C and regulatory A (or PR65) subunits, with each subunit represented by alpha and beta isoforms. Additional regulatory subunits belong to four different families of unrelated proteins. Both the B (or PR55) and B' regulatory protein families contain alpha, beta, gamma and delta isoforms, with the B' family also including an epsilon protein. B'' family proteins include PR72, PR130, PR59 and PR48 isoforms, while striatin (PR110) and SG2NA (PR93) are both members of the B''' regulatory protein family. These B subunits competitively bind to a shared binding site on the core A subunit. This variable array of holoenzyme components, particularly regulatory B subunits, allows PPP2R1A to act in a diverse set of functions. PPP2R1A function is regulated by expression, localization, holoenzyme composition and post-translational modification. Phosphorylation of PPP2R1A at Tyr307 by Src occurs in response to EGF or insulin and results in a substantial reduction of PPP2R1A activity. Reversible methylation on the carboxyl group of Leu309 of PPP2R1A has been observed. Methylation alters the conformation of PPP2R1A, as well as its localization and association with B regulatory subunits.