G-protein coupled receptor 143, GPR143, also known as ocular albinism type 1 protein, OA1, is an orphan GPCR expressed intracellularly in pigment-producing cells on the melanosomal membrane and serves to regulate melanosome size and mediate protein transport to the melanosome via the endolysosomal system.¹

GPR143 is encoded by the OA1 gene, composed of 404 amino acids with 7 transmembrane helices, and associates with several G_α and G_β subunits, as well β-Arrestin. Potential ligands for GPR143 include L-3,4-dihydroxyphenylalanine (L-DOPA) and dopamine. High dose L-DOPA treatment leads to intracellular Ca²⁺ influx and β-Arrestin recruitment. GPR143 has two sorting signals, a dileucine motif in ICL3 and a tryptophan-glutamic acid doublet in the C-terminal tail, which are necessary for lysosomal and melanosomal localization. Functional components of endosomal sorting complexes required for transport (ESCRT) are essential for intracellular sorting and ubiquitination. Due to the unique localization of GPR143 within the cell and its topological orientation, ligands are likely required to bind from the organelle lumen.¹

GPR143 is largely expressed on the melanosomal membrane of melanocytes, the pigment producing cells that are responsible for producing melanin in the skin and eyes. Melanin is a pigment that is crucial for the protection of skin and eyes from damaging UV light, as well as for the normal development of the optic system and eye function. Mutations in the OA1 gene and its subsequent protein products lead to ocular albinism due to melanosome malformation. Albinism is a pigment disorder characterized by decreased melanin in affected tissues, which leads to adverse effects including foveal hypoplasia and chiasmal misrouting.^1,3

GPR143 pathophysiology is also implicated in various degenerative diseases, including macular degeneration and Parkinson’s disease, as well as playing a possible role in cancer susceptibility and progression.^1,2