Several lines of evidence have reported that LGR4–6 enhances activity of Wnt/β-catenin signaling via binding to R-spondins.22, 23, 24 However, LGR5 was found to play a negative role in Wnt signaling in colorectal cancer,32, 33 suggesting that the exact roles of LGR4–6 in Wnt signaling and tumorigenesis appear to vary depending on the given cellular context. Here, LGR5 is linked to colorectal cancer.