Gprc5b, an orphan G-protein-coupled receptor, is involved in multiple biological functions and pathways. It plays a role in regulating autophagy signaling, cell volume regulation, and is associated with pathways like AKT-mTOR-autophagy, NF-κB, and those related to ion channels in astrocytes [1,2]. It is of great biological importance as it impacts various physiological and pathological processes [1-10]. Genetic models, such as knockout mouse models, have been crucial in studying its functions.

In gene knockout studies, Gprc5b-deficient chondrocytes showed up-regulation of cartilage catabolic genes and down-regulation of anabolic genes. Gprc5b-deficient mice had a more severe osteoarthritis (OA) phenotype in the DMM-induced OA model, indicating Gprc5b's role in protecting against OA by regulating autophagy signaling [1]. In podocyte-specific Gprc5b knockout mice, they were partially protected from LPS-induced proteinuria and inflammatory cell recruitment, suggesting Gprc5b modulates inflammatory response in glomerular diseases via the NF-κB pathway [3]. Gprc5b-deficient macrophages showed increased migration and phagocytosis, and in Gprc5b-deficient mice, myeloid cell recruitment was affected in models like myocardial infarction, indicating its role in controlling macrophage function through prostaglandin E receptor 2 signaling [4].

In conclusion, Gprc5b is essential in multiple biological processes. Its knockout mouse models have revealed its significant roles in diseases such as osteoarthritis, glomerular diseases, and macrophage-related pathologies. Understanding Gprc5b through these model-based studies provides insights into the mechanisms of these diseases and potential therapeutic targets.