BACE2 and polycystic kidney disease: In melanocytes, PMEL undergoes a series of proteolytic processing steps, including the cleavage by BACE2 (β-secretase 2) that releases an amyloidogenic Mα fragment into the endosomal lumen (containing N-terminal region (NTR), PKD (polycystic kidney disease domain) and RPT domains), which is further cleaved to produce a fibril-forming CAF (core amyloid fragment) and a fibril-associated RPT fragment32,35–38.