NODAL is a TGFβ superfamily morphogen essential for embryonic patterning and mesoderm specification 1. It signals through Activin type II receptors (ActRIIA/ActRIIB) and type I receptors (ALK4/ALK7), activating Smad2/3-dependent transcription to regulate tissue-specific developmental processes 2. During early development, NODAL establishes left-right asymmetry and cardiac laterality through asymmetric activation in the lateral plate mesoderm, directing Pitx2 expression that patterns visceral organ asymmetry 3. NODAL coordinates multiple developmental mechanisms including concentration-dependent morphogenic signaling, feedback regulation, and interaction with other pathways like Notch3 4. In placental development, NODAL regulates trophoblast invasion, vascularization, and immune tolerance through TGFβ superfamily interactions 5. Notably, pre-implantation pluripotency maintenance in human epiblasts occurs independently of NODAL signaling, contrasting with hESC culture requirements 6. Disease-relevant re-expression of NODAL occurs in adult cancers: in colorectal cancer, NODAL promotes ferroptosis resistance via SCD1-mediated lipid desaturation and Smad2/3 activation, correlating with metastasis 7; in oral squamous cell carcinoma, NODAL co-expression with Cripto-1 associates with advanced disease and invasiveness 8. Heterotaxy mutations in NODAL cause laterality defects, emphasizing its clinical importance in congenital heart disease pathogenesis 4.