Gpr137b, also known as TM7SF1, is an orphan G-protein-coupled receptor. It localizes to the lysosome membrane and is involved in multiple biological processes. It has a role in regulating macrophage polarization, autophagy, and is associated with pathways like the mTORC1-autophagy signaling pathway, which is crucial for cell growth and metabolism [2,3,5].

In a KO mouse model of Gpr137b, deletion led to enhanced autophagy in macrophages and reduced atherosclerotic lesions, characterized by fewer necrotic cores and less lipid accumulation, indicating its role in advanced atherosclerosis progression [1]. In RAW264 mouse macrophage cell line, Gpr137b-KO clones showed reduced IL-4-induced M2 macrophage marker gene expression, suggesting its role in M2 macrophage polarization [2]. In mouse-derived ER-Hoxb8 immortalized myeloid progenitors, decreasing Gpr137b led to increased osteoclast differentiation and bone resorption activity, and gpr137ba-deficient zebrafish also showed increased bone resorption, indicating its role as a negative regulator of osteoclast activity [4].

In conclusion, Gpr137b plays essential roles in macrophage-related functions such as polarization and autophagy, as well as in bone remodeling. The gene knockout models in mice and zebrafish have significantly contributed to understanding its functions in advanced atherosclerosis and bone-related diseases, providing insights into potential therapeutic directions for these conditions.