WNT3A encodes a secreted signaling ligand that functions primarily in the canonical Wnt signaling pathway. The protein requires palmitoleoylation by the enzyme Porcupine for proper function and receptor binding 1. WNT3A binds to Frizzled family receptors, triggering downstream activation of transcription factors in the TCF/LEF family through β-catenin stabilization 2. The protein plays critical roles in embryonic development, particularly in mesoderm formation and neural tube morphogenesis. In disease contexts, WNT3A demonstrates significant clinical relevance across multiple conditions. Elevated WNT3A expression is observed in aganglionic colon segments from Hirschsprung disease patients, with specific gene variants (rs192966556 and rs145882986) conferring increased disease risk 3. WNT3A is implicated in cancer biology, with elevated serum levels detected in non-small cell lung cancer patients alongside multiple gene mutations 4. The protein also shows therapeutic potential, as WNT3A-loaded extracellular vesicles promote alveolar epithelial regeneration and restore pulmonary function in emphysema models 5. Additionally, dysregulated WNT3A expression is associated with chr1 venous insufficiency 6, and it has been proposed as a candidate gene for certain skeletal dysplasias 7.