VANGL1 is a core planar cell polarity (PCP) protein essential for coordinating epithelial cell orientation along the planar axis during development 1. Structurally, VANGL1 oligomerizes as dimers of trimers, with this quaternary organization promoting binding to the PCP effector Prickle1 1. During gastrulation and neurulation, VANGL1 regulates convergent extension movements and apical constriction through non-canonical Wnt/PCP signaling, processes critical for neural tube closure and embryonic axis elongation 2. Dysfunction of VANGL1 is strongly associated with neural tube defects (NTDs). Heterozygous missense mutations occur in approximately 2.1% of spinal NTDs, acting as hypomorphs or conditional mutants predisposing to disease 3. Specific polymorphisms, including rs4839469 (p.Ala116Thr), significantly increase NTD risk through alterations in protein three-dimensional structure 4. VANGL1 mutations also cause congenital vertebral malformations underlying congenital scoliosis 5 and myelomeningocele 6. Beyond developmental disease, VANGL1 promotes cellular motility and invasiveness in cancer through PCP pathway reactivation, with elevated expression in ER-positive breast cancer correlating with poor prognosis 7. These findings establish VANGL1 as a critical regulator of both normal morphogenesis and disease pathogenesis.