Calcium, potassium:sodium antiporter that transports 1 Ca(2+) and 1 K(+) to the melanosome in exchange for 4 cytoplasmic Na(+) (PubMed:18166528). Involved in pigmentation, possibly by participating in ion transport in melanosomes (PubMed:16357253, PubMed:18166528). Predominant sodium-calcium exchanger in melanocytes (PubMed:16357253, PubMed:18166528). Ca(2+)(out) + K(+)(out) + 4 Na(+)(in) = Ca(2+)(in) + K(+)(in) + 4 Na(+)(out) Enriched in late-stage melanosomes. Genetic variants in SLC24A5 define the skin/hair/eye pigmentation variation locus 4 (SHEP4) [MIM:113750]. Hair, eye and skin pigmentation are among the most visible examples of human phenotypic variation, with a broad normal range that is subject to substantial geographic stratification. In the case of skin, individuals tend to have lighter pigmentation with increasing distance from the equator. By contrast, the majority of variation in human eye and hair color is found among individuals of European ancestry, with most other human populations fixed for brown eyes and black hair. The Ala-111 allele predominates (93 to 100%) in African and East Asian populations. In contrast, the Thr-111 allele is nearly fixed (98.7 to 100%) in European populations, is associated with a substantial reduction in regional heterozygosity, and correlates with lighter skin pigmentation in admixed populations. The disease is caused by variants affecting the gene represented in this entry. Belongs to the Ca(2+):cation antiporter (CaCA) (TC 2.A.19) family. SLC24A subfamily. Skin-deep - Issue 74 of September 2006