Researchers may have identified new determinants of human pigmentation, according to a study published by Bajpai et al in Science. The researchers explained that any deviations in melanogenesis may result in disease. They hypothesized that melanin accumulation within the melanosomes could alter the light-scattering capabilities of melanocytes. In the new study, the researchers sought to identify the factors contributing to melanin synthesis within the melanosomes by using flow cytometry to evaluate the light-scattering index—which served as a proxy for the cellular melanin content of the melanocytes as well as an assay for a CRISPR-Cas9–based genetic screen. The researchers analyzed pigmented cell lines and human melanocytes at several stages of development and identified a relationship between melanin levels and the light-scattering index. The researchers discovered 135 new melanin-promoting genes that, when deleted, resulted in decreased melanin production. Two of these genes, KLF6 and COMMD3, were found to be responsible for melanogenesis—and inhibited melanosome maturation, reduced pigmentation, and decreased melanosomal pH when absent. Additionally, in darker pigmented human melanocytes, the expression of the genes was elevated. The researchers hope their new findings can establish a resource for future studies analyzing the associations between melanogenesis, skin pigmentation, and diseases.