PPP2R5A (protein phosphatase 2 regulatory subunit B'alpha) encodes a regulatory subunit of protein phosphatase 2A (PP2A) that modulates the cellular location, substrate specification, and phosphatase function of the PP2A holoenzyme 1. The protein is highly expressed in cardiac and skeletal muscle and localizes to chromosome 1 2. PPP2R5A plays crucial roles in multiple cellular processes through its regulation of PP2A activity. In cancer biology, PPP2R5A functions as a tumor suppressor by enabling PP2A to dephosphorylate oncogenic targets like c-Myc, with small molecules that stabilize the B56α-PP2A complex showing therapeutic potential 3. The protein's function can be disrupted in pancreatic cancer, where HMGA2 downregulates PPP2R5A expression, impairing PP2A holoenzyme assembly and promoting increased mRNA translation through sustained S6K phosphorylation 4. PPP2R5A is also involved in metabolic regulation, as its knockdown significantly decreases adipocyte lipidation and alters expression of key adipogenesis genes including DGAT2, LPL, and PPARG 5. Additionally, PPP2R5A expression is regulated during inflammatory responses, where its downregulation increases PP2A activity and promotes dephosphorylation of NF-κB and MAPK signaling pathways 6. The protein can be targeted for degradation by HIV-1 Vif, which disrupts both PP2A assembly and substrate binding 7.