PRICKLE3 is an X-linked protein with dual roles in planar cell polarity (PCP) signaling and mitochondrial function. As a core PCP module component, PRICKLE3 localizes to cell junctions where it stabilizes VANGL1/2 proteins by protecting them from CK1ε-mediated phosphorylation and RNF43-mediated degradation 1. It interacts with apical determinant Par3 to promote asymmetric distribution of PCP complexes during neurulation 2. Additionally, PRICKLE3 regulates basal body organization and cilia growth in cooperation with Wtip 3. Beyond PCP, PRICKLE3 is essential for mitochondrial ATP synthase (complex V) assembly, stability, and function through direct interaction with ATP8 4. PRICKLE3 also participates in canonical WNT signaling by facilitating DVL2 deubiquitination through USP9X interaction, promoting NSCLC progression 5. Clinically, PRICKLE3 variants act as X-linked modifiers of Leber hereditary optic neuropathy (LHON). The p.Arg53Trp mutation synergizes with mitochondrial ND4 11778G>A mutations to cause severe mitochondrial dysfunction and retinal ganglion cell degeneration 46. PRICKLE3 upregulation occurs during dental papilla cell polarization via JNK signaling 7. The protein's diverse functions link developmental morphogenesis with mitochondrial homeostasis and cancer progression.