Leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4)

Leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4) is a transmembrane receptor of the G protein-coupled receptor (GPCR) superfamily, subfamily B. It acts as a key modulator of the Wnt/β-catenin signaling pathway, which is critical for stem cell maintenance, organogenesis, and tissue homeostasis. LGR4 binds classical ligands such as R-spondins (RSPO1-4) and Norrin, and is also recognized as an alternative receptor for RANKL, exerting inhibitory control over osteoclast differentiation and bone resorption. Besides its developmental roles in kidney, eye, reproductive tract, intestine, and liver, LGR4 is implicated in regulation of energy metabolism, inflammation, circadian rhythms, and adipogenesis. LGR4 dysregulation is associated with diverse human diseases, including cancer, osteoporosis, metabolic and endocrine disorders, and various inflammatory conditions. Its multifunctionality and tissue distribution present both opportunities and challenges for therapeutic targeting[1][2][3][4][5][6].

Other names

G protein-coupled receptor 48GPR48LGR4Leucine-rich repeat-containing G-protein coupled receptor 4

Agonism or antagonism of LGR4 modulates Wnt/β-catenin signaling, alters stem cell dynamics, or inhibits osteoclastogenesis (especially in the context of R-spondin or RANKL interaction)[1][2]. - Agents antagonizing LGR4-RANKL interaction could inhibit osteoclast differentiation and bone resorption[1].