A recent study demonstrated that the protein phosphatase, pleckstrin homology domain leucine-rich repeat protein phosphatase 2 (PHLPP2), was downregulated in UC and regulated GSDMD-induced intestinal epithelial cells (IECs) pyroptosis by modulating the NF-κB signaling, and PHLPP2 depletion increased the susceptibility to colitis by inducing dramatic activation of caspase-1/GSDMD in IECs (47). The gene discussed is GSDMD; the disease is colitis.