PPP2CB encodes the beta catalytic subunit of protein phosphatase 2A (PP2A), a critical serine/threonine phosphatase that regulates diverse cellular processes. As part of heterotrimeric PP2A complexes, PPP2CB catalyzes protein dephosphorylation and participates in STRIPAK complexes that regulate multiple signaling pathways including Hippo, MAPK, and cytoskeleton remodeling 1. PPP2CB demonstrates significant disease relevance across multiple pathological contexts. In atherosclerosis, PPP2CB expression is upregulated in peripheral blood leukocytes of patients and arterial plaques, where it exacerbates lipid accumulation through interaction with LOX-1 and activation of MAPK/ERK signaling 2. In sepsis-related acute lung injury, PPP2CB is identified as a hub gene with elevated expression 3. PPP2CB also regulates autophagy through LC3B dephosphorylation, reducing mitophagy efficiency and contributing to neuronal toxicity in spinocerebellar ataxia type 12 1. In vascular smooth muscle cells, PPP2CB acts downstream of YAP1/TEAD1 transcriptional control to inhibit AMPK and activate mTORC1, promoting cell proliferation 4. Clinically, high PPP2CB expression correlates with poor prognosis in pancreatic cancer, while in colon cancer it appears protective 56. These findings establish PPP2CB as a versatile regulator with context-dependent roles in disease pathogenesis.