PRICKLE4 is a planar cell polarity (PCP) protein that functions as a regulator of the non-canonical WNT/PCP signaling pathway, which governs cell polarity, tissue architecture, and coordinated cell movements 1. As a member of the PRICKLE protein family characterized by conserved LIM domains and a PET domain 2, PRICKLE4 localizes to the nucleus and is broadly expressed across tissues. At the molecular level, PRICKLE proteins function within the WNT/PCP pathway by modulating interactions between core pathway components 1. PRICKLE4 is highly expressed in aggressive Stem-A subtype ovarian cancer cells, where it participates in PCP-mediated regulation of actin cytoskeleton reorganization, cell polarity, and RhoA/Rac1 signaling 3. In glioma biology, PRICKLE4 plays a critical role in driving microenvironmental remodeling and promoting angiogenesis, thereby mediating resistance to PARP inhibitor therapy 4. Targeting PRICKLE4 effectively overcomes PARP inhibitor resistance in IDH-mutant gliomas 4. These findings establish PRICKLE4 as a functionally important regulator of cell polarity signaling with significant implications for cancer biology and therapeutic resistance.