GPR143 is an atypical G protein-coupled receptor primarily involved in melanocyte function and retinal development. As an L-DOPA and dopamine receptor 1, GPR143 stimulates calcium influx and activates G(q)-mediated phosphoinositide signaling pathways in melanocytic cells, promoting secretion of the neurotrophic factor SERPINF1 [UniProt]. Beyond pigmentation, GPR143 functions as an intracellular GPCR controlling ESCRT-dependent exosome biogenesis through interactions with the HRS complex, regulating selective protein sorting into multivesicular bodies 2. Mutations in GPR143 cause X-linked ocular albinism (XLOA), characterized by foveal hypoplasia, reduced vision, nystagmus, and variable iris/fundus hypopigmentation 3. The disease affects only ocular tissues despite normal melanin synthesis, suggesting a tissue-specific developmental role 4. While XLOA is nonprogressive and vision remains stable throughout life 5, the retinal pathology reflects disrupted RPE-retinal interactions during development 6. Additionally, GPR143 regulates dopamine D2 receptor function in striatal cholinergic interneurons, influencing antipsychotic-induced motor side effects 1. Beyond Mendelian disease, GPR143 is elevated in multiple cancers where it promotes exosome-mediated metastasis through integrin/FAK/Src signaling 2, suggesting broader pathophysiological roles in both developmental and oncogenic processes.