Adgrg6, also known as GPR126, is an adhesion G protein-coupled receptor. It is crucial in developmental processes such as Schwann cell maturation and inner ear morphogenesis in zebrafish embryos [1,2]. It is involved in cell-cell and cell-extracellular matrix interactions, playing significant roles in many physiological and pathological processes [2]. Genetic models like the zebrafish are valuable for studying Adgrg6.

In zebrafish, homozygous adgrg6 hypomorphic mutants have been used as a screening platform. These mutants have helped identify candidate molecules that can influence Adgrg6 signaling activity and rescue mutant phenotypes, offering promise as small-molecule modulators of the Adgrg6 pathway [1]. In human, mutations in ADGRG6 can lead to severe deficits in peripheral myelination, and variants are associated with diseases like chronic obstructive pulmonary disease (COPD), lung cancer, bladder cancer, and arthrogryposis multiplex congenita [1,3,4,5,6]. In iPSC-derived type II alveolar epithelial cells, ADGRG6 knockdown affects functions like focal adhesions, cytoskeleton, tight junctions, and proliferation, as well as cellular responses to injury [3].

In conclusion, Adgrg6 is essential for developmental processes and has implications in multiple disease conditions. Studies using models like zebrafish adgrg6 mutants have been instrumental in uncovering its role in biological processes and disease. The findings suggest that Adgrg6 could be a potential target for therapeutic intervention in diseases such as those related to peripheral myelination, COPD, and certain cancers.