Receptor for R-spondins that potentiates the canonical Wnt signaling pathway and is involved in the formation of various organs. Upon binding to R-spondins (RSPO1, RSPO2, RSPO3 or RSPO4), associates with phosphorylated LRP6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes. In contrast to classical G-protein coupled receptors, does not activate heterotrimeric G-proteins to transduce the signal. Its function as activator of the Wnt signaling pathway is required for the development of various organs, including liver, kidney, intestine, bone, reproductive tract and eye. May also act as a receptor for norrin (NDP), such results however require additional confirmation in vivo. Required during spermatogenesis to activate the Wnt signaling pathway in peritubular myoid cells. Required for the maintenance of intestinal stem cells and Paneth cell differentiation in postnatal intestinal crypts. Acts as a regulator of bone formation and remodeling. Involved in kidney development; required for maintaining the ureteric bud in an undifferentiated state. Involved in the development of the anterior segment of the eye. Required during erythropoiesis. Also acts as a negative regulator of innate immunity by inhibiting TLR2/TLR4 associated pattern-recognition and pro-inflammatory cytokine production. Plays an important role in regulating the circadian rhythms of plasma lipids, partially through regulating the rhythmic expression of MTTP (PubMed:24353284). Required for proper development of GnRH neurons (gonadotropin-releasing hormone expressing neurons) that control the release of reproductive hormones from the pituitary gland (PubMed:32493844). During limb development, at 14.5 dpc, expressed in the mesenchyme, but not in the overlying ectoderm of the limb bud. In developing lungs, at 14.5 dpc, expressed at low levels in both the epithelium and mesenchyme lineages. Expressed in a circadian manner in the liver. Strong variations in phenotypes, probably depending on the strain background used in the different experiments. According to a first report done in a C57BL/6 background, mice show intra-uterine growth retardation leading to embryonic and perinatal lethality (PubMed:15192078). A lethal phenotype was confirmed by other groups. In some cases however, few mice survive until adulthood. Mice that survive show wide spectrum of anterior segment dysgenesis phenotypes, including microphthalmia, iris hypoplasia, irdiocorneal angle malformation, cornea dysgenesis and cataract (PubMed:18424556). Defects in osteoblast differentiation and mineralization during embryonic bone formation are also observed. Postnatal mice that survive show defects in bone remodeling (PubMed:19605502). According to other reports done in other strain backgrounds, mice do not die and display defects in the male reproductive tract during the postnatal period (PubMed:16406039, PubMed:17079737, PubMed:23533175). Mice also show small kidneys, in which the total number and density of the glomeruli are decreased (PubMed:16785743). The use of conditional knockouts, leads to defects in hair placode formation, possibly due to reduced keratinocyte migration (PubMed:17079737, PubMed:17850793). Decrease in epithelial cell proliferation and strong reduction in terminal differentiation of Paneth cells in postnatal intestinal crypts (PubMed:21508962, PubMed:23393138). Fetuses display transient anemia during midgestation and abnormal definitive erythropoiesis (PubMed:18955481). Mice are also more susceptible and have much higher mortality to lipopolysaccharide (LPS) stimulation due to over-activated innate immune response (PubMed:23589304). Conditional knockout of both Lgr4 and Lgr5 in the gut results in Wnt signaling inhibition and results in the rapid demise of intestinal crypts (PubMed:21727895). Simultaneous knockdown of LGR4, LGR5 and LGR6 results in developmental phenotypes, such as cleft palate and ankyloglossia, but not in tetra-amelia with lung agenesis (PubMed:29769720). Belongs to the G-protein coupled receptor 1 family.