Interestingly, a cohort of lysosomal integral membrane proteins became enriched on the cell surface in VPS35 KO H4 cells, including the lysosomal glycocalyx components LAMP1 and LAMP2, the cholesterol transporter NPC1, the Juvenile Neuronal Ceroid Lipofuscinosis associated CLN3, CI-MPR (IGF2R), and a cluster of APP processing-related proteins including APP, the β-secretase BACE2, the APP-like protein and β-secretase substrates APLP1 and APLP257, and APP-binding protein ITM2B58,59 (Fig. 4d). The gene discussed is IGF2R; the disease is juvenile neuronal ceroid lipofuscinosis.