G-protein coupled receptor which is activated by type IV collagen, a major constituent of the basement membrane. Essential for normal differentiation of promyelinating Schwann cells and for normal myelination of axons these functions are mediated via G-protein-signaling pathways (PubMed:24227709, PubMed:21613327). Regulates also neural, cardiac and ear development via G-protein- and/or N-terminus-dependent signaling. May act as a receptor for PRNP which may promote myelin homeostasis (PubMed:27501152). Plays an important role in heart developmention (PubMed:24082093). Necessary and sufficient for axon sorting by Schwann cells independently of the ADGRG6-CTF (PubMed:25695270). Interacts with Laminin-2; this interaction stabilizes the receptor in an inactive state (PubMed:25695270). Laminin-2 polymerization could facilitate ADGRG6-NTF removal, thereby exposing the tethered agonist to drive myelination (PubMed:25695270). Interacts with PRNP (PubMed:27501152). Expressed at high levels in the heart, somite and otic vesicle during embryogenesis and in adult lung. Proteolytically cleaved into 2 conserved sites: one in the GPS domain (S1 site) and the other in the middle of the extracellular domain (S2 site). The proteolytic cleavage at S1 site generates an N-terminal fragment (NTF) and a seven-transmembrane-containing C-terminal fragment (CTF). The membrane-bound CTF can act as an independent receptor and the soluble NTF can act as a ligand or coreceptor. Furin is involved in the cleavage of the S2 site generating a soluble fragment. Processing at the GPS domain occurred independent of and probably prior to the cleavage at the S2 site. Proteolytic cleavage is required for activation of the receptor (By similarity). Deficient mice die during organogenesis. Mutant embryos show signs of myocardial wall thinning, hypotrabeculation, defective mitochondrial and circulatory failure. Belongs to the G-protein coupled receptor 2 family. Adhesion G-protein coupled receptor (ADGR) subfamily.