LGR5

LGR5 (Leucine-rich repeat-containing G-protein coupled receptor 5), also known as GPR49 or FEX, is a member of the rhodopsin-like GPCR family characterized by its large extracellular leucine-rich repeat domain. It functions as a high-affinity receptor for R-spondin (RSPO) proteins, acting as a co-receptor to amplify Wnt/β-catenin signaling by stabilizing the Frizzled-LRP5/6 complex. This mechanism is critical for maintaining stem cell populations in intestinal crypts, hair follicles, and other regenerative tissues. Dysregulated LGR5 expression is implicated in colorectal cancer, gastric cancer, and hepatocellular carcinoma, where it marks tumor-initiating cells with enhanced self-renewal capacity. Its role in tissue repair has spurred interest in targeting LGR5+ stem cells for regenerative therapies. Pharmaceutical efforts focus on developing monoclonal antibodies and small-molecule inhibitors against LGR5-positive cancer stem cells, though challenges remain in achieving tumor-specific targeting while sparing normal stem cell niches. Recent preclinical studies have explored bispecific antibodies engaging LGR5 and immune checkpoint molecules.