LGR4

LGR4, or leucine-rich repeat-containing G protein-coupled receptor 4, is a member of the LGR family of receptors. It is a G protein-coupled receptor characterized by a large extracellular leucine-rich repeat domain and seven transmembrane regions. The LGR4 gene encodes this receptor, which is expressed in multiple tissues, including the intestinal epithelium, skin, and developing organs.

Functionally, LGR4 serves as a receptor for the secreted RSPO proteins (R-spondins 1–4). Binding of RSPOs to LGR4 potentiates canonical Wnt/β-catenin signaling by antagonizing the activity of the E3 ubiquitin ligases ZNRF3 and RNF43, which promote degradation of Wnt receptors. This mechanism increases the cell-surface abundance of Frizzled receptors and enhances Wnt pathway activity.

Biologically, the RSPO-LGR4 signaling axis supports stem cell maintenance and proliferation in tissues such as the intestinal crypts and contributes to organ development and tissue homeostasis. LGR4 is also implicated in bone remodeling and hair follicle biology in various model systems, reflecting broader roles in tissue regeneration and development.

In clinical and research contexts, dysregulation of LGR4 signaling has been linked to disease processes, including cancer and degenerative conditions. Because of its central role in modulating Wnt signaling and stem cell dynamics, LGR4 is a focus of investigations into regenerative medicine and cancer therapeutics.