LGR5 (leucine-rich repeat-containing G-protein-coupled receptor 5) serves as a critical stem cell marker and Wnt signaling regulator across multiple tissues. In the intestinal epithelium, LGR5 marks cycling columnar cells at the crypt base that function as adult stem cells, generating all epithelial lineages over extended periods 1. These LGR5+ stem cells maintain close physical associations with Paneth cells, which provide essential niche signals including EGF, TGF-α, Wnt3, and Dll4 necessary for stem cell maintenance 2. Beyond normal tissue homeostasis, LGR5+ cells serve as cancer stem cells in colorectal tumors, demonstrating self-renewal and differentiation capacity while driving tumor growth 3. Interestingly, metastatic spread is primarily initiated by LGR5- cells that subsequently acquire LGR5+ cancer stem cell properties upon establishing distant metastases 4. LGR5 expression extends to other tissues, including specialized fibroblasts in lung airways that form signaling hubs 5 and skin fibroblasts that become dysregulated in scleroderma 6. The therapeutic targeting of LGR5+ cancer stem cells shows promise, with bispecific antibodies demonstrating efficacy against EGFR×LGR5 in epithelial tumors while sparing healthy stem cells 7.