PMEL (premelanosome protein) is a melanocyte-specific scaffolding protein essential for melanosome biogenesis and pigmentation. Located on chromosome 12-q13, PMEL functions primarily in organizing melanin synthesis through formation of specialized fibrillar structures 1. Mechanistically, PMEL assembles into highly organized lamellar sheets composed of laterally aligned fibrils with butterfly-shaped units containing proteolytically cleaved Mα and Mβ fragments arranged in amyloid-like β-sheet conformations 2. These physiological amyloid fibrils optimize melanin sequestration and condensation within melanosomes 3. PMEL fibril formation requires C-mannosylation at multiple tryptophan residues; mutations disrupting this modification impair fibril assembly and cause endoplasmic reticulum retention and lysosomal misaggregation 4. The repeat domain (RPT) acts accessorily to control amyloid formation 5. Disease relevance includes oculocutaneous albinism (OCA), where loss-of-function PMEL variants cause hypopigmentation 6, and pigment dispersion syndrome (PDS), where the G175S mutation hyperactivates amyloidogenesis, increasing extracellular amyloid load 7. Additionally, PMEL serves as a potent melanoma-specific immunodominant antigen, with multiple peptide epitopes stimulating HLA-A-restricted cytotoxic T cell responses, making it clinically significant for immunotherapy development.