PPP1CA (protein phosphatase 1 catalytic subunit alpha) is a major serine/threonine phosphatase that regulates diverse cellular processes through protein dephosphorylation 1. The enzyme functions as part of holoenzyme complexes with regulatory subunits that determine substrate specificity and cellular localization 1. In transcriptional regulation, PPP1CA within the PNUTS-PP1 complex promotes RNA polymerase II pause release by dephosphorylating multiple substrates including MEPCE, thereby sustaining global transcriptional activation 2. The phosphatase plays critical roles in cancer progression through multiple mechanisms. In hepatocellular carcinoma, PPP1CA promotes tumorigenesis by dephosphorylating YAP1, facilitating its nuclear translocation and activation of Hippo pathway target oncogenes 3. Similarly, in colorectal cancer, PPP1CA stabilization leads to YAP dephosphorylation and enhanced tumor progression 4. In renal cancer, PPP1CA interaction with the PDHK1-241aa peptide inhibits AKT dephosphorylation, activating the AKT-mTOR pathway 5. PPP1CA also regulates autophagy through TFEB dephosphorylation, with methylation at K141 by SUV39H2 disrupting this function in intervertebral disc degeneration 6. These findings establish PPP1CA as a key regulatory phosphatase with significant therapeutic potential across multiple diseases.