PPP2R5C encodes the B56γ regulatory subunit of protein phosphatase 2A (PP2A), a trimer complex that opposes serine/threonine kinase signaling 1. As a regulatory subunit, PPP2R5C modulates substrate selectivity, catalytic activity, and subcellular localization of the PP2A holoenzyme, with roles in dephosphorylating and inactivating growth-promoting kinases in the PIK3CA/AKT/mTOR and RAS/MAPK pathways 1. PPP2R5C plays critical roles in cell proliferation, differentiation, and apoptosis; knockdown suppresses proliferation and induces apoptosis through altered MAPK, PI3K/AKT, and JAK/STAT pathway signaling 2. PPP2R5C is significantly overexpressed in multiple leukemia types and associated with malignant transformation in B-cell chr14 lymphocytic leukemia 3. Pathogenic variants in PPP2R5C cause Houge-Janssens syndrome type 4, characterized by neurodevelopmental delay, hypotonia, seizures, and behavioral problems 4. These variants predominantly affect substrate binding or catalytic subunit interaction, likely operating through dominant-negative mechanisms 4. PPP2R5C genetic variants also associate with residual disease in ovarian cancer 5, and a related long non-coding RNA (LincR-PPP2R5C) regulates IL-1β ubiquitination in COPD pathogenesis 6. PPP2R5C methylation status shows promise for colorectal cancer screening 7.