Premelanosome protein (PMEL) (PMEL)

The premelanosome protein, known as PMEL or PMEL17, is an integral membrane glycoprotein essential for the structural formation of intralumenal fibrils in early-stage (stage I and II) premelanosomes within melanocytes. These fibrils provide a matrix for melanin deposition during eumelanogenesis, determining the elliptical shape of melanosomes, and PMEL achieves this through proteolytic processing of its lumenal domain into fibrillogenic fragments after endosomal sorting. Synthesized in the endoplasmic reticulum, PMEL traffics via the Golgi and endosomes, where it invaginates into intralumenal vesicles, distinguishing premelanosomes as a unique lineage separate from conventional lysosomes and endosomes. Mutations or truncations in PMEL, as seen in the silver mouse model, disrupt fibril formation, leading to enlarged, rounded melanosomes and hypopigmentation phenotypes. While primarily expressed in pigmented cells, PMEL detection in non-pigmented bovine tissues suggests potential broader roles, though unconfirmed, and it serves as a melanoma tumor marker due to melanocyte-specific expression. No drugs directly target PMEL, and its manipulation primarily affects pigmentation rather than serving as a therapeutic target in diseases beyond color dilution traits.

Other names

PMEL17gp100SILVsilverME20Pmel-17