LGR6 is a leucine-rich repeat containing G protein-coupled receptor that functions as a receptor for R-spondin ligands and plays critical roles in stem cell biology and tissue homeostasis. Upon binding to R-spondins (RSPO1-4), LGR6 potentiates canonical Wnt signaling by associating with phosphorylated LRP6 and frizzled receptors 1. This receptor operates through a non-equivalent but cooperative mechanism with Wnt ligands, where Wnt proteins maintain basal competency by sustaining RSPO receptor expression, while R-spondins actively drive stem cell expansion 1. LGR6 serves as a stem cell marker in various tissues and demonstrates protective functions in cardiovascular disease by suppressing necroptosis through Wnt-mediated regulation of STAT2 and ZBP1 expression 2. Additionally, LGR6 functions as a receptor for maresin-1, a pro-resolving lipid mediator that enhances phagocyte functions including phagocytosis and efferocytosis, contributing to inflammation resolution 3. In cancer contexts, LGR6 expression is associated with stemness subtypes and poor prognosis in esophageal squamous cell carcinoma 4. The receptor's expression is regulated by DNA methylation, with hypomethylation patterns observed in ankylosing spondylitis patients 5.