{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:07:47Z","timestamp":1791846467827,"version":"4.3.4"},"reference-count":227,"publisher":"The Endocrine Society","issue":"4","license":[{"start":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T00:00:00Z","timestamp":1676419200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012149","name":"National Key R&D Program of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012149","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,7,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Classic hormone membrane receptors, such as leucine-rich repeat-containing G protein\u2013coupled receptor (LGR) 1 (follicle-stimulating hormone receptor), LGR2 (luteinizing hormone receptor), and LGR3 (thyrotropin receptor), are crucial in endocrinology and metabolism, and the identification of new receptors can advance this field. LGR4 is a new member of this G protein\u2013coupled receptor family and shows ways of expression and function similar to those of LGR1\/2\/3. Several recent studies have reported that, unlike LGR5\/6, LGR4 plays essential roles in endocrine and metabolic diseases, including hypothalamic\u2013gonadal axis defects, mammary gland dysplasia, osteoporosis, cardiometabolic diseases, and obesity. An inactivating mutation p.R126X in LGR4 leads to osteoporosis, electrolyte disturbance, abnormal sex hormone levels, and weight loss, whereas an activating mutation p.A750T is associated with bone mineral density, insulin resistance, and adiposity. Though several paracrine ligands are known to act on LGR4, the endocrine ligands of LGR4 remain poorly defined. In this review, we highlight LGR4 dysfunction in clinical diseases, animal models, and pathophysiological changes, discuss their known ligands and downstream signaling pathways, and identify unresolved questions and future perspectives of this new receptor.<\/jats:p>","DOI":"10.1210\/endrev\/bnad003","type":"journal-article","created":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T17:59:17Z","timestamp":1676483957000},"page":"647-667","source":"Crossref","is-referenced-by-count":37,"title":["LGR4: A New Receptor Member in Endocrine and Metabolic Diseases"],"prefix":"10.1210","volume":"44","author":[{"given":"Ningning","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (SJTUSM) , Shanghai 200025 , China"},{"name":"Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, SJTUSM , Shanghai 200025 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyang","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (SJTUSM) , Shanghai 200025 , China"},{"name":"Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, SJTUSM , Shanghai 200025 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9383-7656","authenticated-orcid":false,"given":"Jiqiu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (SJTUSM) , Shanghai 200025 , China"},{"name":"Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, SJTUSM , Shanghai 200025 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2023,2,15]]},"reference":[{"issue":"12","key":"2023071114163442300_bnad003-B1","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1210\/mend.12.12.0211","article-title":"Characterization of two LGR genes homologous to gonadotropin and thyrotropin receptors with extracellular leucine-rich repeats and a G protein-coupled, seven-transmembrane region","volume":"12","author":"Hsu","year":"1998","journal-title":"Mol Endocrinol"},{"issue":"2","key":"2023071114163442300_bnad003-B2","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1006\/bbrc.1998.8774","article-title":"Identification and cloning of an orphan G protein-coupled receptor of the glycoprotein hormone receptor subfamily","volume":"247","author":"McDonald","year":"1998","journal-title":"Biochem Biophys Res 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