PARD6B (par-6 family cell polarity regulator beta) is a scaffold protein located on chromosome 20 that functions as a node within the Par protein complex, primarily regulating cell polarity and epithelial organization 1. It operates mechanistically as part of the PAR6B-PRKCI-PAR3 complex, linking GTP-bound Rho small GTPases to atypical protein kinase C proteins and contributing to tight junction assembly and apico-basal polarization 2. PARD6B is essential for normal alveolar epithelial cell proliferation, maintaining cell cycle progression and preventing G0-G1 arrest 2. Disease relevance is complex and context-dependent. In colorectal cancer, PARD6B acts as an oncogene—its chromosome 20 amplification correlates with high expression, which independently predicts poor prognosis by upregulating MYC expression and suppressing miR-34c 1. Similarly, downregulation of the PKCζ/Pard3/Pard6b complex in lung adenocarcinoma drives epithelial-mesenchymal transition, invasion, and chemoresistance 3. Conversely, in chr20 obstructive pulmonary disease emphysema, reduced PARD6B impairs alveolar regeneration by arresting type II alveolar epithelial cell proliferation 2. PARD6B also plays roles in retinal regeneration and maintaining epithelial integrity in age-related macular degeneration 45. These findings suggest PARD6B functions dually—as a tumor suppressor when maintaining epithelial polarity, but paradoxically as an oncogene when dysregulated in specific cancer contexts 6.