# Adhesion G-Protein Coupled Receptors in Neurological and Psychiatric Disorders **Authors:** Brandon H. Lee, Christina M. Meyer, David J. Speca, Elva Díaz PMC · DOI: 10.20900/jpbs.20250017 · Journal of psychiatry and brain science · 2026-02-21 ## TL;DR This paper reviews how adhesion G-protein coupled receptors are involved in brain functions and linked to neurological and psychiatric disorders. ## Contribution The paper provides a comprehensive review of aGPCRs' roles in brain functions and their associations with neurological and psychiatric diseases. ## Key findings - aGPCRs are involved in neurodevelopment, synapse formation, and blood-brain barrier establishment. - Dysfunction of aGPCRs is linked to disorders like gliomas, depression, and epilepsy. - aGPCRs are potential targets for future pharmacological treatments. ## Abstract The adhesion G-protein coupled receptors (aGPCRs) are a family of 33 G-protein receptors consisting of ADGRA1–3, ADGRB1–3, ADGRC1–3, ADGRD1–2, ADGRE1–5, ADGRF1–5, ADGRG1–7, ADGRL1–4, and ADGRV1. Recent studies have unveiled the role of aGPCRs in numerous brain functions, including in neurodevelopment, synapse formation and maintenance, establishment of the blood-brain barrier, and myelination. Further, dysfunction of aGPCRs have been associated with disorders such as gliomas, depression, and epilepsy, among many others. Herein, we review generalized properties of aGPCRs, their brain-specific expression, associations with neurological and psychiatric diseases, and potential as future pharmacological targets. ## Linked entities - **Genes:** ADGRA1 (adhesion G protein-coupled receptor A1) [NCBI Gene 84435], ADGRA2 (adhesion G protein-coupled receptor A2) [NCBI Gene 25960], ADGRA3 (adhesion G protein-coupled receptor A3) [NCBI Gene 166647], ADGRB1 (adhesion G protein-coupled receptor B1) [NCBI Gene 575], ADGRB2 (adhesion G protein-coupled receptor B2) [NCBI Gene 576], ADGRB3 (adhesion G protein-coupled receptor B3) [NCBI Gene 577], CELSR1 (cadherin EGF LAG seven-pass G-type receptor 1) [NCBI Gene 9620], CELSR2 (cadherin EGF LAG seven-pass G-type receptor 2) [NCBI Gene 1952], CELSR3 (cadherin EGF LAG seven-pass G-type receptor 3) [NCBI Gene 1951], ADGRD1 (adhesion G protein-coupled receptor D1) [NCBI Gene 283383], ADGRD2 (adhesion G protein-coupled receptor D2) [NCBI Gene 347088], ADGRE1 (adhesion G protein-coupled receptor E1) [NCBI Gene 2015], ADGRE2 (adhesion G protein-coupled receptor E2) [NCBI Gene 30817], ADGRE3 (adhesion G protein-coupled receptor E3) [NCBI Gene 84658], Adgre4 (adhesion G protein-coupled receptor E4) [NCBI Gene 52614], ADGRE5 (adhesion G protein-coupled receptor E5) [NCBI Gene 976], ADGRF1 (adhesion G protein-coupled receptor F1) [NCBI Gene 266977], ADGRF2P (adhesion G protein-coupled receptor F2, pseudogene) [NCBI Gene 222611], ADGRF3 (adhesion G protein-coupled receptor F3) [NCBI Gene 165082], ADGRF4 (adhesion G protein-coupled receptor F4) [NCBI Gene 221393], ADGRF5 (adhesion G protein-coupled receptor F5) [NCBI Gene 221395], ADGRG1 (adhesion G protein-coupled receptor G1) [NCBI Gene 9289], ADGRG2 (adhesion G protein-coupled receptor G2) [NCBI Gene 10149], ADGRG3 (adhesion G protein-coupled receptor G3) [NCBI Gene 222487], ADGRG4 (adhesion G protein-coupled receptor G4) [NCBI Gene 139378], ADGRG5 (adhesion G protein-coupled receptor G5) [NCBI Gene 221188], ADGRG6 (adhesion G protein-coupled receptor G6) [NCBI Gene 57211], ADGRG7 (adhesion G protein-coupled receptor G7) [NCBI Gene 84873], ADGRL1 (adhesion G protein-coupled receptor L1) [NCBI Gene 22859], ADGRL2 (adhesion G protein-coupled receptor L2) [NCBI Gene 23266], ADGRL3 (adhesion G protein-coupled receptor L3) [NCBI Gene 23284], ADGRL4 (adhesion G protein-coupled receptor L4) [NCBI Gene 64123], ADGRV1 (adhesion G protein-coupled receptor V1) [NCBI Gene 84059] - **Diseases:** depression (MONDO:0002050), epilepsy (MONDO:0005027) ## Full-text entities - **Genes:** Glul (glutamate-ammonia ligase) [NCBI Gene 14645] {aka GS, Glns}, DOCK1 (dedicator of cytokinesis 1) [NCBI Gene 1793] {aka DOCK180, ced5}, ADGRG7 (adhesion G protein-coupled receptor G7) [NCBI Gene 84873] {aka GPR128}, ADGRF5 (adhesion G protein-coupled receptor F5) [NCBI Gene 221395] {aka GPR116, KPG_001}, Flrt3 (fibronectin leucine rich transmembrane protein 3) [NCBI Gene 71436] {aka 5530600M07Rik, C430047I10Rik, mKIAA1469}, CKAP5 (cytoskeleton associated protein 5) [NCBI Gene 9793] {aka CHTOG, MSPS, TOG, TOGp, ch-TOG}, ADGRB1 (adhesion G protein-coupled receptor B1) [NCBI Gene 575] {aka BAI1, GDAIF}, TENM3 (teneurin transmembrane protein 3) [NCBI Gene 55714] {aka MCOPCB9, MCOPS15, ODZ3, TEN3, TNM3, Ten-m3}, Par3 (pulmonary adenoma resistance 3) [NCBI Gene 112235], ADGRE5 (adhesion G protein-coupled receptor E5) [NCBI Gene 976] {aka CD97, TM7LN1}, Clrn1 (clarin 1) [NCBI Gene 229320] {aka A130002D11Rik, USH3, Ush3a, clarin-1}, NFIA (nuclear factor I A) [NCBI Gene 4774] {aka BRMUTD, C1DELp32p31, CTF, DEL1P32P31, NF-I/A, NF1-A}, ADGRL2 (adhesion G protein-coupled receptor L2) [NCBI Gene 23266] {aka CIRL2, CL2, LEC1, LPHH1, LPHN2}, FN1 (fibronectin 1) [NCBI Gene 2335] {aka CIG, ED-B, FINC, FN, FNZ, GFND}, ADGRF1 (adhesion G protein-coupled receptor F1) [NCBI Gene 266977] {aka GPR110, KPG_012, PGR19, hGPCR36}, Mdm2 (MDM2 proto-oncogene) [NCBI Gene 17246] {aka 1700007J15Rik, Mdm-2}, Prnp (prion protein) [NCBI Gene 19122] {aka CD230, PrP, PrP, PrPC, PrPSc, Prn-i}, GNA13 (G protein subunit alpha 13) [NCBI Gene 10672] {aka G13, HG1N}, Adgrl1 (adhesion G protein-coupled receptor L1) [NCBI Gene 330814] {aka 2900070I05Rik, CLIBA, Lec2, Lphn1, mKIAA0821}, Tgfb2 (transforming growth factor, beta 2) [NCBI Gene 21808] {aka Tgf-beta2, Tgfb-2}, Arhgef11 (Rho guanine nucleotide exchange factor 11) [NCBI Gene 213498] {aka PDZ-RhoGEF, Prg, RhoGEF, mKIAA0380}, Daam1 (dishevelled associated activator of morphogenesis 1) [NCBI Gene 208846], ADGRG4 (adhesion G protein-coupled receptor G4) [NCBI Gene 139378] {aka GPR112, PGR17, RP1-299I16}, Adgrg6 (adhesion G protein-coupled receptor G6) [NCBI Gene 215798] {aka 1190004A11Rik, DREG, Gm222, Gpr126}, Mbd2 (methyl-CpG binding domain protein 2) [NCBI Gene 17191] {aka MBD2a}, PXN (paxillin) [NCBI Gene 5829], Ctnnb1 (catenin beta 1) [NCBI Gene 12387] {aka Bfc, Catnb, Mesc}, Rho (rhodopsin) [NCBI Gene 212541] {aka Noerg1, Opn2, Ops, RP4}, OXT (oxytocin/neurophysin I prepropeptide) [NCBI Gene 5020] {aka OT, OT-NPI, OXT-NPI}, ADGRA1 (adhesion G protein-coupled receptor A1) [NCBI Gene 84435] {aka GPR123}, Adcy6 (adenylate cyclase 6) [NCBI Gene 11512] {aka AC6, mKIAA0422}, ADGRG1 (adhesion G protein-coupled receptor G1) [NCBI Gene 9289] {aka BFPP, BPPR, CDCBM14B, CDCBM15A, GPR56, TM7LN4}, Pdzd7 (PDZ domain containing 7) [NCBI Gene 100503041] {aka 9130207N01, EG435601, Pdzk7}, Cdc42 (cell division cycle 42) [NCBI Gene 12540], Kdr (kinase insert domain protein receptor) [NCBI Gene 16542] {aka 6130401C07, Flk-1, Flk1, Krd-1, Ly73, VEGFR-2}, Adgrl2 (adhesion G protein-coupled receptor L2) [NCBI Gene 99633] {aka CIRL-2, Gm619, Lec1, Lphh1, Lphn2, mKIAA0786}, Cdh23 (cadherin related 23 (otocadherin)) [NCBI Gene 22295] {aka 4930542A03Rik, USH1D, ahl, ahl1, bob, bus}, Dock1 (dedicator of cytokinesis 1) [NCBI Gene 330662] {aka 9130006G06Rik, D630004B07Rik, b2b3190Clo}, Tcp1 (t-complex protein 1) [NCBI Gene 21454] {aka CCT, Cct1, Ccta, TRic, Tcp-1, Tp63}, Cct3 (chaperonin containing TCP1 subunit 3) [NCBI Gene 12462] {aka Cctg, Tcp1-rs3, TriC-P5}, Gata2 (GATA binding protein 2) [NCBI Gene 14461] {aka Gata-2}, Hspd1-ps3 (heat shock protein 1 (chaperonin), pseudogene 3) [NCBI Gene 432551] {aka Gm12141, Hspd1-1p}, Pvalb (parvalbumin) [NCBI Gene 19293] {aka PV, Parv, Pva}, Adgrb3 (adhesion G protein-coupled receptor B3) [NCBI Gene 210933] {aka A830096D10Rik, Bai3}, ADGRA3 (adhesion G protein-coupled receptor A3) [NCBI Gene 166647] {aka GPR125, PGR21, TEM5L}, MYCN (MYCN proto-oncogene, bHLH transcription factor) [NCBI Gene 4613] {aka FGLDS1, MODED, MPAPA, MYCNsORF, MYCNsPEP, N-myc}, Adgrg1 (adhesion G protein-coupled receptor G1) [NCBI Gene 14766] {aka Cyt28, Gpr56, TM7LN4, TM7XN1}, SNAP25 (synaptosome associated protein 25) [NCBI Gene 6616] {aka CMS18, DEE117, RIC-4, RIC4, SEC9, SNAP}, ADGRG2 (adhesion G protein-coupled receptor G2) [NCBI Gene 10149] {aka CBAVDX, EDDM6, GPR64, HE6, TM7LN2}, Sst (somatostatin) [NCBI Gene 20604] {aka SOM, SRIF, SS, Smst}, Gpc3 (glypican 3) [NCBI Gene 14734] {aka OCI-5}, Ezh2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) [NCBI Gene 14056] {aka Enx-1, Enx1h, KMT6, mKIAA4065}, Vezt (vezatin, adherens junctions transmembrane protein) [NCBI Gene 215008] {aka A630071D13Rik}, RHO (rhodopsin) [NCBI Gene 6010] {aka CSNBAD1, OPN2, RP4}, GLP1R (glucagon like peptide 1 receptor) [NCBI Gene 2740] {aka GLP-1, GLP-1-R, GLP-1R}, AVP (arginine vasopressin) [NCBI Gene 551] {aka ADH, ARVP, AVP-NPII, AVRP, VP}, Memo1 (mediator of cell motility 1) [NCBI Gene 76890] {aka 0610016J10Rik, D930048L02Rik}, Tiam1 (T cell lymphoma invasion and metastasis 1) [NCBI Gene 21844] {aka D16Ium10, D16Ium10e}, ADGRA2 (adhesion G protein-coupled receptor A2) [NCBI Gene 25960] {aka GPR124, TEM5}, pcp (polydactyly with cleft palate) [NCBI Gene 18543] - **Diseases:** taste perception (MESH:D013651), Glioma (MESH:D005910), common carotid artery occlusion (MESH:D002340), epilepsy (MESH:D004827), HBD (MESH:C563602), metastases (MESH:D009362), idiopathic scoliosis (MESH:D012600), distal arthrogryposis (MESH:C535378), spina bifida (MESH:D016135), neurodegeneration (MESH:D019636), cerebral vascularization defects (MESH:D002532), inflammation (MESH:D007249), embryonic lethality (MESH:D020964), central hypotonia (MESH:D009123), nerve injury (MESH:D000080902), Usher syndrome (MESH:D052245), Parkinson's disease (MESH:D010300), peripheral nerve injuries (MESH:D059348), Myelination defects (MESH:D003711), ASD (MESH:D000067877), intellectual disability (MESH:D008607), brain injury (MESH:D001930), impaired vision (MESH:D014786), ADHESION (MESH:D000267), shoulder and neck pain (MESH:D020069), cerebral ischemia (MESH:D002545), endothelial dysfunction (MESH:D014652), cerebral ischemic injury (MESH:D017202), Huntington's disease (MESH:D006816), congenital contracture syndrome 9 (OMIM:616503), cancer (MESH:D009369), ear dysfunction (MESH:D004427), ischemic stroke (MESH:D002544), audiogenic seizures (MESH:D020195), degeneration of hearing and vision (MESH:D054062), ADHD (MESH:D001289), Neurological and Psychiatric Disorders (MESH:D001523), Tourette's syndrome (MESH:D005879), -PROTEIN COUPLED (MESH:D011488), substance use disorder (MESH:D019966), deafness (MESH:D003638), Alzheimer's disease (MESH:D000544), cerebral and cerebellar atrophy (OMIM:615760), neuroendocrine carcinoma (MESH:D018278), cognitive and language development delay (MESH:D007805), edema (MESH:D004487), defects in the vestibular system (MESH:D020338), anxiety (MESH:D001007), schizophrenia (MESH:D012559), falciparum malaria (MESH:D016778), Neuroinflammation (MESH:D000090862), cannabis use disorder (MESH:D002189), cortex (MESH:D000303), BBB damage (MESH:C536830), TBI (MESH:D000070642), BBS (MESH:D049932), impaired vestibular-ocular reflexes (MESH:D015837), Rubinstein-Taybi syndrome (MESH:D012415), patchy neuropathy (MESH:C531609), megalencephaly-capillary malformation polymicrogyria syndrome (MESH:C566381) - **Chemicals:** Ca2+ (-), Oxygen (MESH:D010100), sodium (MESH:D012964), retinoic acid (MESH:D014212), methylphenidate (MESH:D008774), duloxetine (MESH:D000068736), phosphatidylserine (MESH:D010718), nicotine (MESH:D009538), lipopolysaccharide (MESH:D008070), sucrose (MESH:D013395), amphetamine (MESH:D000661), Synaptamide (MESH:C000628804), morphine (MESH:D009020), dopamine (MESH:D004298), calcium (MESH:D002118), serotonin (MESH:D012701) - **Species:** Danio rerio (leopard danio, species) [taxon 7955], Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Paracentrotus lividus (common sea urchin, species) [taxon 7656], C. elegans [taxon 328850], Drosophila melanogaster (fruit fly, species) [taxon 7227] - **Mutations:** A/G, rs6551665, rs1397547, rs4044210, rs1109581, R1465W, p.R271*, c.2219T > A, rs6007897 ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12922695/full.md ## Figures 3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12922695/full.md ## References 516 references — full list in the complete paper: https://tomesphere.com/paper/PMC12922695/full.md --- Source: https://tomesphere.com/paper/PMC12922695