Slc45a2 and V‐ATPase are regulators of melanosomal pH homeostasis in zebrafish, providing a mechanism for human pigment evolution and disease

Summary We present here the positional cloning of the D anio rerio albino mutant and show that the affected gene encodes S lc45a2. The human orthologous gene has previously been shown to be involved in human skin color variation, and mutations therein have been implicated in the disease OCA 4. Through ultrastructural analysis of the melanosomes in albino alleles as well as the tyrosinase‐deficient mutant sandy , we add new insights into the role of S lc45a2 in the production of melanin. To gain further understanding of the role of S lc45a2 and its possible interactions with other proteins involved in melanization, we further analyzed the role of the V ‐ ATP ase as a melanosomal acidifier. We show that it is possible to rescue the melanization potential of the albino melanosomes through genetic and chemical inhibition of V ‐ ATP ase, thereby increasing internal melanosome p H .