Aberrant Wnt/R-spondin/ZNRF3 signaling is implicated in tumorigenesis, where 7% of colon cancer and 31% of serrated adenoma samples harbor RSPO3 gene fusions with the neighboring Protein tyrosine phosphatase receptor-type kappa (PTPRK) gene (Seshagiri et al., 2012; Sekine et al., 2016). Here, ZNRF3 is linked to colonic neoplasm.