PKHD1 and polycystic kidney disease: Fibrocystin is one such Notch-like protein in animals associated with polycystic kidney disease that is known to be first translated as a membrane protein and then proteolytically processed—probably by a proprotein convertase and ADAM metalloproteinase disintegrins—into N and C-terminal fragments that translocate away from the membrane into other compartments, with the C-terminus trafficking into the nucleus (Hiesberger et al, 2006; Kaimori et al, 2007; Follit et al, 2010).