{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T23:56:14Z","timestamp":1788998174083,"version":"build-2803163510"},"reference-count":68,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,5,16]],"date-time":"2022-05-16T00:00:00Z","timestamp":1652659200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004837","name":"MICINN","doi-asserted-by":"publisher","award":["RTI2018-093493-B-I00"],"award-info":[{"award-number":["RTI2018-093493-B-I00"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare type of vacuolating leukodystrophy (white matter disorder), which is mainly caused by defects in MLC1 or glial cell adhesion molecule (GlialCAM) proteins. In addition, autoantibodies to GlialCAM are involved in the pathology of multiple sclerosis. MLC1 and GLIALCAM genes encode for membrane proteins of unknown function, which has been linked to the regulation of different ion channels and transporters, such as the chloride channel VRAC (volume regulated anion channel), ClC-2 (chloride channel 2), and connexin 43 or the Na+\/K+-ATPase pump. However, the mechanisms by which MLC proteins regulate these ion channels and transporters, as well as the exact function of MLC proteins remain obscure. It has been suggested that MLC proteins might regulate signalling pathways, but the mechanisms involved are, at present, unknown. With the aim of answering these questions, we have recently described the brain GlialCAM interactome. Within the identified proteins, we could validate the interaction with several G protein-coupled receptors (GPCRs), including the orphan GPRC5B and the proposed prosaposin receptors GPR37L1 and GPR37. In this review, we summarize new aspects of the pathophysiology of MLC disease and key aspects of the interaction between GPR37 receptors and MLC proteins.<\/jats:p>","DOI":"10.3390\/ijms23105528","type":"journal-article","created":{"date-parts":[[2022,5,16]],"date-time":"2022-05-16T13:06:23Z","timestamp":1652706383000},"page":"5528","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["GPR37 Receptors and Megalencephalic Leukoencephalopathy with Subcortical Cysts"],"prefix":"10.3390","volume":"23","author":[{"given":"Adri\u00e0","family":"Pla-Casillanis","sequence":"first","affiliation":[{"name":"Unitat de Fisiologia, Departament de Ci\u00e8ncies Fisiol\u00f2giques, Genes Disease and Therapy Program IDIBELL-Institute of Neurosciences, Universitat de Barcelona, L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Ferigle","sequence":"additional","affiliation":[{"name":"Unitat de Fisiologia, Departament de Ci\u00e8ncies Fisiol\u00f2giques, Genes Disease and Therapy Program IDIBELL-Institute of Neurosciences, Universitat de Barcelona, L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Alonso-Gard\u00f3n","sequence":"additional","affiliation":[{"name":"Unitat de Fisiologia, Departament de Ci\u00e8ncies Fisiol\u00f2giques, Genes Disease and Therapy Program IDIBELL-Institute of Neurosciences, Universitat de Barcelona, L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Efren","family":"Xicoy-Espaulella","sequence":"additional","affiliation":[{"name":"Unitat de Fisiologia, Departament de Ci\u00e8ncies Fisiol\u00f2giques, Genes Disease and Therapy Program IDIBELL-Institute of Neurosciences, Universitat de Barcelona, L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaitz","family":"Errasti-Murugarren","sequence":"additional","affiliation":[{"name":"Unitat de Gen\u00e8tica, Departament de Ci\u00e8ncies Fisiol\u00f2giques, Genes Disease and Therapy Program IDIBELL-Institute of Neurosciences, Universitat de Barcelona, L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n en Red de Enfermedades Raras (CIBERER), ISCIII, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1582-9271","authenticated-orcid":false,"given":"Daniela","family":"Marazziti","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Cell Biology, Italian National Research Council (CNR), I-00015 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1579-650X","authenticated-orcid":false,"given":"Ra\u00fal","family":"Est\u00e9vez","sequence":"additional","affiliation":[{"name":"Unitat de Fisiologia, Departament de Ci\u00e8ncies Fisiol\u00f2giques, Genes Disease and Therapy Program IDIBELL-Institute of Neurosciences, Universitat de Barcelona, L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n en Red de Enfermedades Raras (CIBERER), ISCIII, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/S1474-4422(12)70192-8","article-title":"Megalencephalic leukoencephalopathy with subcortical cysts: Chronic white matter oedema due to a defect in brain ion and water homoeostasis","volume":"11","author":"Boor","year":"2012","journal-title":"Lancet Neurol."},{"key":"ref_2","unstructured":"Knaap, M.S., van der Abbink, T.E.M., and Min, R. 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