PARD3 (par-3 family cell polarity regulator) functions as a master regulator of cell polarity and asymmetric cell division, playing critical roles in both normal development and disease pathogenesis 1. As a scaffolding protein, PARD3 forms complexes with PARD6 and atypical protein kinase C (aPKC) to establish and maintain epithelial polarity, including tight junction formation and proper cellular organization 23. The protein regulates macropinocytosis during metabolic stress through aPKC signaling and Par3 relocation to microtubules 3. In neuronal development, PARD3 cooperates with JamC to promote germinal zone exit through Netrin-1 signaling pathways 4. Clinically, PARD3 exhibits dual functionality in cancer, acting as either tumor suppressor or promoter depending on cellular context 1. In hepatocellular carcinoma, PARD3 overexpression promotes tumorigenesis by activating Sonic Hedgehog signaling in tumor-initiating cells and interacting with the DCAF1/Akt pathway 56. Loss of PARD3 polarity correlates with hepatocyte depolarization and poor prognosis 7. Conversely, in gliomas, PARD3 functions as a tumor suppressor by regulating RhoA through aPKC/NF-κB signaling 8. These findings establish PARD3 as a critical regulator of cellular organization with significant therapeutic implications.