MREG Human

Melanoregulin is involved in the regulation of melanosome size and distribution. It interacts with members of the Hermansky-Pudlak Syndrome (HPS) BLOC-2 complex and the ocular albinism 1 (Oa1) protein, which are essential for melanosome biogenesis . In the absence of MREG, there is an increase in the size of micromelanosomes in the choroid of HPS BLOC-2 mutants, while overexpression of MREG corrects the size of retinal pigment epithelium (RPE) macromelanosomes in Oa1 knockout mice .

MREG is also required for lysosome maturation and function. It modulates lysosome-dependent phagosome degradation, and its deficiency leads to the accumulation of phagosomes due to delayed degradation of engulfed material . This results in the accumulation of lipofuscin components, such as A2E, in retinal pigment epithelial cells . MREG-deficient cells exhibit diminished activity of the lysosomal hydrolase, cathepsin D, due to defective processing .

Immunohistochemical analysis has shown that melanoregulin localizes to small vesicles in the cytoplasm of RPE cells, suggesting a role in regulating membrane interactions during melanosome biogenesis . It also associates with the endosomal phosphoinositide, phosphatidylinositol 3,5-biphosphate, indicating its involvement in intracellular trafficking .

The understanding of MREG’s role in organelle biogenesis and lysosome function provides a foundation for potential therapeutic approaches to correct pigment defects in conditions such as Hermansky-Pudlak Syndrome and ocular albinism . By modulating MREG levels, it may be possible to restore normal melanosome size and function, thereby addressing the pigmentation abnormalities associated with these disorders .