WNT8B encodes a secreted glycoprotein ligand that activates frizzled family receptors to transduce canonical Wnt signaling 1. The gene maps to chromosome 10 and is expressed in multiple fetal and adult tissues 1. WNT8B plays critical roles in nervous system development, particularly thalamus patterning and neural progenitor cell differentiation 2, with c-JUN identified as a key transcriptional regulator of WNT8B expression. The protein undergoes context-dependent signaling to activate downstream targets including MYC and CCND1, and can also activate non-canonical pathways involving RHOA and JNK 3. WNT8B dysregulation associates with multiple cancers. In hepatocellular carcinoma, elevated WNT8B expression correlates with poor prognosis and is transcriptionally regulated by zinc finger protein ZNF191, promoting cell proliferation via canonical Wnt signaling 4. High WNT8B expression independently predicts reduced survival in nasopharyngeal carcinoma 5. WNT8B mutations and aberrant expression occur in Hirschsprung disease, suggesting developmental significance 6. Expression is hormonally regulated—upregulated by β-estradiol in breast cancer cells and downregulated by retinoic acid during neuronal differentiation 7. Copy number loss at WNT8B occurs in undifferentiated pleomorphic sarcoma 8, indicating tumor-suppressive potential in specific contexts.