ADGRG6, also known as GPR126, is a member of the adhesion class of G-protein coupled receptors (aGPCRs). aGPCRs are characterized by a 7 transmembrane-spanning domain that couples to G-protein signaling and an extracellular N-terminal extension that mediates cell-cell or cell-matrix adhesion (reviewed in Langenhan et al, 2013). Like most aGPCRs, ADGRG6 is subject to autocatalytic processing during maturation, yielding a C-terminal fragment containing the 7-TM region, and an N-terminal fragment containing the extracellular region. Cleavage occurs at the conserved GPCR proteolytic site (GPS), part of the larger GPCR autoproteolysis-inducing (GAIN) domain (Moriguchi et al, 2004; Arac et al, 2012). As with other aGPCRs, these two domains remain associated in a heterodimer at the plasma membrane where they mediate signaling and cell adhesion (Moriguchi et al 2004; Arac et al, 2012; Lin et al, 2004; reviewed in Langenhan et al, 2013; Mehta et al, 2017).