MLPH

Mlph, short for melanophilin, is a gene that encodes a cytosolic adaptor protein involved in the intracellular transport of melanosomes in pigment-producing cells. In vertebrates it functions as a Rab27A effector that helps coordinate the peripheral distribution of pigment-containing organelles necessary for normal pigmentation.

Mechanistically, melanophilin forms a tripartite complex with Rab27A on melanosomes and with the motor protein myosin Va. This Rab27A–melanophilin–myosin Va axis links melanosomes to the actin cytoskeleton, enabling their movement to the cell periphery where pigments are transferred into growing keratinocytes or dispersed within pigment cells. The proper functioning of this transport system is essential for uniform pigment distribution in skin, hair, and eyes.

Genetic and clinical significance is most clearly illustrated in humans by Griscelli syndrome type 3, caused by mutations in MLPH. GS3 is characterized by hypopigmentation, typically affecting hair and skin, with no major neurological or immunological deficits. In mice and other model organisms, Mlph mutations produce dilute fur or coat color due to impaired melanosome transport, providing a basis for studying pigment cell biology. Population-level variation in MLPH can also contribute to natural pigment diversity without causing disease.

Evolution and models show that the Mlph-mediated transport mechanism is conserved across vertebrates, underlining its fundamental role in pigment cell biology. Research using Mlph-deficient animals continues to illuminate how intracellular transport controls pigmentation and how disruptions lead to color disorders.