PDZ binding kinase (PBK) is a serine/threonine kinase primarily active during mitosis that phosphorylates MAP kinase p38 and regulates cell cycle progression 1. PBK functions as a cell proliferation driver through phosphorylation of PRC1, promoting cytokinesis and G2/M phase progression 2. When phosphorylated, PBK forms complexes with TP53, attenuating G2/M checkpoint control during DNA damage [UniProt]. Mechanistically, PBK phosphorylates key regulatory proteins including TRIM37 (promoting NFκB pathway activation) 1 and TIPE2 (regulating ubiquitin-mediated degradation) 3, while interacting with PRC1 to modulate cytokinesis 2. Clinically, PBK dysregulation drives multiple malignancies. Elevated PBK expression confers PARP inhibitor resistance in ovarian cancer through TRIM37/NFκB axis activation and associates with poor prognosis in medulloblastoma and pituitary neuroendocrine tumors 145. In pulmonary arterial hypertension, PBK upregulation in pulmonary artery smooth muscle cells promotes pathological vascular remodeling; PBK inhibition or genetic knockout prevented disease development in animal models 2. PBK also regulates neuroinflammation by disrupting TIPE2 interactions, with PBK inhibition reducing lipopolysaccharide-induced microglial activation 3. These findings establish PBK as a therapeutic target across cancer, cardiovascular, and neuroinflammatory diseases.