The B regulatory subunit might modulate substrate selectivity and catalytic activity, and also might direct the localization of the catalytic enzyme to a particular subcellular compartment. Within the PP2A holoenzyme complex, isoform 2 is required to promote proapoptotic activity. Isoform 2 regulates neuronal survival through the mitochondrial fission and fusion balance. PP2A consists of a common heterodimeric core enzyme, composed of a 36 kDa catalytic subunit (subunit C) and a 65 kDa constant regulatory subunit (PR65 or subunit A), that associates with a variety of regulatory subunits. Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules (By similarity). Interacts with IER5 (via N- and C-terminal regions) (By similarity). Interacts with TOMM22 (PubMed:15923182). Under basal conditions, localizes to both cytosolic and mitochondrial compartments. Relocalizes from the cytosolic to the mitochondrial compartment during apoptosis. Its targeting to the outer mitochondrial membrane (OMM) involves an association with import receptors of the TOM complex and is required to promote proapoptotic activity. Expressed in the brain. Isoform 1 and isoform 2 are expressed in the forbrain. Isoform 1 is more strongly expressed than isoform 2 in the olfactory bulb. Isoform 1 and isoform 2 are weakly expressed in the cerebellum. Isoform 1 is expressed in the testis. Isoform 2 expression is undetectable at birth rising to adult level at day 14. Up-regulated postnatally and in response to neuronal differentiation. The N-terminal 26 residues of isoform 2 constitute a cryptic mitochondrial matrix import signal with critical basic and hydrophobic residues, that is necessary and sufficient for targeting the PP2A holoenzyme to the outer mitochondrial membrane (OMM) and does not affect holoenzyme formation or catalytic activity. The last WD repeat of isoform 2 constitutes a mitochondrial stop-transfer domain that confers resistance to the unfolding step process required for import and therefore prevents PPP2R2B matrix translocation and signal sequence cleavage. Contains a cryptic mitochondrial transit peptide at positions 1-23. Mutagenesis of Lys-2 to Ala greatly reduces interaction with TOMM22, the outer mitochondrial membrane (OMM) localization and proapoptotic activity. Mutagenesis of Arg-6 to Ala greatly reduces outer mitochondrial membrane (OMM) localization and proapoptotic activity. Combined mutagenesis of Thy-7 and Leu-8 to Ala or Thy-10 and Ile-11 and Phe-12 to Ala or Ile-18 and Leu-19 to Ala strongly impaired mitochondrial localization and proapoptotic activity. Mutagenesis of Arg-13 to Ala does not inhibit OMM localization and proapoptotic activity. Mutagenesis of Cys-3 to Ala or Ser does not inhibit OMM localization and proapoptotic activity. Mutagenesis of Phe-4 to Ala or Thy-7 to Ala or Leu-8 to Ala or Tyr-10 to Ala or Ile-11 to Ala or Phe-12 to Ala weakly impaired mitochondrial localization and proapoptotic activity. Belongs to the phosphatase 2A regulatory subunit B family.