PPP2CA encodes the catalytic α-subunit of protein phosphatase 2A (PP2A), a major serine/threonine phosphatase that regulates diverse cellular processes through substrate dephosphorylation 1. As the catalytic component of PP2A holoenzyme complexes, PPP2CA functions within various regulatory complexes including STRIPAK and INTAC complexes to control multiple signaling pathways including PIK3CA/AKT/mTOR, RAS/MAPK, Wnt, and Hippo signaling 12. The enzyme dephosphorylates numerous substrates involved in cell cycle regulation, transcriptional control, and metabolic processes 34. PPP2CA plays critical roles in tumor suppression by regulating immune signaling pathways, including cGAS-STING-type I interferon signaling in glioblastoma 5. Loss-of-function mutations in PPP2CA cause Houge-Janssens syndrome type 3, characterized by neurodevelopmental delay, hypotonia, seizures, and behavioral problems due to PP2A dysfunction and altered growth-promoting kinase activity 1. The protein is also implicated in cardiovascular disease progression through extracellular vesicle-mediated signaling 2 and cancer metabolic reprogramming via lactate-driven pathways 3. PPP2CA represents a potential therapeutic target, as compounds like triptolide can modulate its activity to suppress tumor progression 3.