NKD1 (NKD inhibitor of Wnt signaling pathway 1) is a cell autonomous antagonist that primarily functions as a negative regulator of the canonical Wnt/β-catenin signaling pathway 12. The protein contains an EF-hand motif within its NH2 domain and can bind to Dishevelled proteins to inhibit Wnt signaling 3. However, NKD1 exhibits complex and context-dependent functions, as it can also promote non-canonical Wnt signaling pathways controlling planar cell polarity 3. In cancer contexts, NKD1 demonstrates paradoxical roles. Its expression is frequently downregulated in osteosarcoma and hepatocellular carcinoma, where reduced levels correlate with tumor progression, metastasis, and poor differentiation 12. Conversely, in colon cancer, NKD1 promotes tumor progression through non-Wnt mechanisms by preventing autophagic degradation of MYC protein and enhancing glucose uptake via YWHAE transcriptional activation 45. NKD1 is regulated by epigenetic modifications, including m6A methylation mediated by YTHDF3, which suppresses NKD1 expression and activates Wnt/β-catenin signaling in hepatocellular carcinoma 6. These findings suggest NKD1 serves as both a tumor suppressor and oncogene depending on cancer type and cellular context.