PABIR1 (FAM122A) is an intrinsically disordered protein that functions as an endogenous inhibitor of protein phosphatase 2A (PP2A), specifically the PP2A:B55α complex 1. PABIR1 inhibits PP2A through a competitive mechanism: it contains conserved helical motifs ([RK]-V-x-x-[VI]-R) that bind to B55α and block substrate docking sites while spatially constraining access to the catalytic subunit 23. By inhibiting PP2A-mediated dephosphorylation of WEE1, PABIR1 promotes WEE1 ubiquitin-dependent degradation and facilitates G2/M checkpoint release during mitotic entry 4. PABIR1 also potentiates PP2A catalytic subunit degradation through increased poly-ubiquitination 1. Functionally, PABIR1 is essential for cell cycle progression through G1/S and intra-S checkpoints, and its deletion impairs checkpoint control in response to replication stress 3. Clinically, PABIR1 expression correlates with cancer cell proliferation and survival: it is upregulated in hepatocellular carcinoma, and its deletion enhances chemotherapy sensitivity 5. PABIR1 expression levels serve as a biomarker for predicting CHK1 inhibitor sensitivity in tumor cells 4.