Beyond the classic GPCR: unraveling the role of GPR155 role in cholesterol sensing and signaling

In a recent cryo-EM study published in Nature, Bayly-Jones and co-workers have provided detailed molecular insights into the dimerization and cholesterol binding of the orphan G protein-coupled receptor GPR155, its potential involvement in gut microbiota-derived tryptophan metabolite interactions, and intracellular signaling pathways.¹ GPR155, a lysosomal protein with a unique 17-transmembrane helix domain structure, integrates auxin transporter and G protein-coupled receptor-like features, playing a key role in lysosomal cholesterol sensing and mTORC1 signaling.