PRICKLE1 is a planar cell polarity (PCP) pathway component that regulates convergent extension during gastrulation and neural tube closure 1. The protein functions in the non-canonical Wnt/PCP signaling axis, where it acts as a proteasomal target of Wnt5a signaling and is necessary for proper nuclear localization of the transcription factor REST 23. Mechanistically, PRICKLE1 interacts with Dishevelled proteins and regulates cell polarity machinery to control tissue morphogenesis 2. PRICKLE1 dysfunction is associated with multiple developmental disorders. Loss-of-function mutations cause neural tube defects and recapitulate features of Robinow syndrome 42. The R104Q mutation, identified in progressive myoclonic epilepsy patients, impairs interaction between PRICKLE1 and REST, resulting in reduced excitatory synapse density, decreased seizure threshold, and autism-spectrum behaviors 5. PRICKLE1 variants also predispose to cleft palate, independent of Vangl2 function 6. Additionally, PRICKLE1 may serve as a biomarker in ankylosing spondylitis, where promoter hypomethylation correlates with elevated mRNA expression 7, and mutations are identified as prospective biomarkers for EZH2 inhibitor resistance in SMARCB1-deficient sarcomas 8.