SLC24A5 encodes a potassium-dependent sodium-calcium exchanger that functions as a calcium, potassium:sodium antiporter, transporting 1 Ca2+ and 1 K+ to melanosomes in exchange for 4 cytoplasmic Na+ 1. The protein serves as the predominant sodium-calcium exchanger in melanocytes and plays a crucial role in pigmentation by participating in ion transport within melanosomes, likely by maintaining melanosomal pH during melanogenesis 12. Loss-of-function variants in SLC24A5 cause oculocutaneous albinism type 6 (OCA6), characterized by reduced pigmentation in skin, hair, and eyes, along with ocular abnormalities including nystagmus, strabismus, and foveal hypoplasia 32. The rs1426654 polymorphism (G>A) within SLC24A5 represents one of the most significant genetic contributors to human skin color variation, with the A allele strongly associated with lighter pigmentation across populations 45. This polymorphism shows dramatic frequency differences between populations and serves as a major ancestry informative marker, contributing to the evolutionary adaptation to different UV environments 6. Functional studies demonstrate that SLC24A5 variants affect melanin content and melanosome development, confirming its essential role in normal pigmentation 78.