SLC45A2 encodes a membrane-associated transporter protein that functions primarily in melanocyte pigmentation through regulation of melanosome pH. The protein localizes to mature melanosomes and functions as a proton/glucose exporter that increases lumenal pH by decreasing glycolysis 1. SLC45A2 operates later in melanosome maturation than OCA2, maintaining melanosome neutralization initially established by transient OCA2 activity to support proper tyrosinase function and melanin synthesis 1. Mutations in SLC45A2 cause oculocutaneous albinism type 4 (OCA4), which accounts for approximately 12.6% of Chinese OCA cases 2 and represents one of four major OCA subtypes 3. A common polymorphism L374F (rs16891982) significantly influences normal pigmentation variation, with the L374 variant associated with darker pigmentation and increased melanoma risk, while F374 is associated with lighter pigmentation and reduced melanoma risk 45. The F374 variant shows reduced protein stability due to rapid proteasome-dependent degradation, resulting in lower melanosomal protein levels compared to L374 1. This functional difference explains the population-specific pigmentation associations observed across different ethnic groups 6.