{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n G protein‐coupled receptor 137B (GPR137B) is an orphan receptor that has emerged as a key regulator of lysosome‐based signaling and cellular homeostasis. In cultured human cells and zebrafish models, GPR137B localizes to the lysosomal membrane where it interacts with Rag GTPases. This interaction enhances Rag localization and activity, thereby promoting the recruitment and activation of mTORC1—even under amino acid–deprived conditions—and regulates the cycle of Rag dissociation from lysosomes. Loss of GPR137B function results in impaired autophagy and an expanded lysosomal compartment, underscoring its importance in maintaining normal lysosome morphology and autolysosome degradation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In parallel, studies focusing on osteoclast biology have revealed that GPR137B is highly expressed in osteoclasts, where its expression increases during differentiation. Functional analyses using gene disruption approaches indicate that deficiency of GPR137B leads to enhanced osteoclast differentiation and increased bone-resorbing activity. These findings suggest that, under physiological conditions, GPR137B may act to restrain osteoclast maturation and temper bone resorption."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, high-throughput deorphanization efforts have characterized the G protein coupling profile of several orphan receptors, including GPR137B, thereby linking its activity to various pathophysiological processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In addition, genetic association studies have identified replication signals in regions near GPR137B in rheumatoid arthritis, highlighting a potential role of this receptor in inflammatory disease susceptibility."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, GPR137B functions as a lysosome-associated regulatory protein that modulates mTORC1 signaling and autophagy through its interaction with Rag GTPases and may additionally influence osteoclast differentiation and inflammatory disease risk. Its emerging roles make GPR137B a promising target for further research into therapies for metabolic, skeletal, and inflammatory disorders.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Lin Gan, Akiko Seki, Kimberle Shen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The lysosomal GPCR-like protein GPR137B regulates Rag and mTORC1 localization and activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41556-019-0321-6"}], "href": "https://doi.org/10.1038/s41556-019-0321-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31036939"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31036939"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "K Urso, J Caetano-Lopes, P Y Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A role for G protein-coupled receptor 137b in bone remodeling in mouse and zebrafish."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bone (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bone.2019.06.002"}], "href": "https://doi.org/10.1016/j.bone.2019.06.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31173907"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31173907"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Lyndsay R Watkins, Cesare Orlandi "}, {"type": "b", "children": [{"type": "t", "text": "In vitro profiling of orphan G protein coupled receptor (GPCR) constitutive activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Pharmacol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/bph.15468"}], "href": "https://doi.org/10.1111/bph.15468"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33784795"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33784795"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jan Freudenberg, Hye-Soon Lee, Bok-Ghee Han, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide association study of rheumatoid arthritis in Koreans: population-specific loci as well as overlap with European susceptibility loci."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arthritis Rheum (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/art.30235"}], "href": "https://doi.org/10.1002/art.30235"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21452313"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21452313"}]}]}]}