Lgr4/GPR48 Protein, Human (HEK293, His)

The Lgr4/GPR48 Protein functions as the receptor for R-spondins, actively potentiating the canonical Wnt signaling pathway and contributing to the formation of various organs. Upon binding to R-spondins (RSPO1, RSPO2, RSPO3, or RSPO4), Lgr4/GPR48 associates with phosphorylated LRP6 and frizzled receptors activated by extracellular Wnt, instigating the canonical Wnt signaling cascade and upregulating the expression of target genes. Distinguished from classical G-protein coupled receptors, Lgr4/GPR48 does not activate heterotrimeric G-proteins for signal transduction. Its pivotal role as a Wnt signaling pathway activator is indispensable for the development of diverse organs, including the liver, kidney, intestine, bone, reproductive tract, and eye. Additionally, Lgr4/GPR48 may function as a receptor for norrin (NDP), with in vivo confirmation needed. It is essential during spermatogenesis for activating the Wnt signaling pathway in peritubular myoid cells and is required for maintaining intestinal stem cells, Paneth cell differentiation, kidney development, anterior eye segment development, proper bone formation, and remodeling. Furthermore, Lgr4/GPR48 acts as a negative regulator of innate immunity by inhibiting TLR2/TLR4-associated pattern recognition and pro-inflammatory cytokine production. Its regulatory role extends to the circadian rhythms of plasma lipids, partially through the rhythmic expression of MTTP, and it is essential for the proper development of GnRH neurons, which control the release of reproductive hormones from the pituitary gland.