ADGRG6 (adhesion G protein-coupled receptor G6), also known as GPR126, is an adhesion GPCR that functions as a receptor for steroid hormones, particularly progesterone and 17α-hydroxyprogesterone 1. Upon ligand binding, ADGRG6 undergoes conformational changes that trigger G protein signaling, primarily coupling to Gi proteins to inhibit adenylate cyclase, though it can also couple to Gq proteins 1. The receptor modulates downstream effectors including adenylate cyclase and SRC kinases 1. ADGRG6 has critical developmental roles in peripheral nervous system myelination, where it is required for Schwann cell differentiation and normal axon myelination 2. Beyond neurodevelopment, ADGRG6 regulates bone mass and body length, and participates in blood-brain barrier formation via interactions with LRP1 and ITGB1 3. In pathological contexts, ADGRG6 is associated with lethal congenital contracture syndrome 9 and arthrogryposis multiplex congenita 4. Additionally, progesterone-activated ADGRG6 promotes breast cancer cell growth through Gi-SRC signaling pathways 1. Genome-wide association studies implicate ADGRG6 in chr6 obstructive pulmonary disease and reduced lung function, with functional studies demonstrating its role in alveolar epithelial cell homeostasis and injury response 5. ADGRG6 expression is also altered in multiple kidney diseases, suggesting therapeutic potential 6.