Figure 8.

Figure 8. Proposed changes induced by CLN3 deficiency along the endolysosomal pathway

In healthy cells, the number of intraluminal vesicles (ILVs) increases in the early endosomes to form multilamellar bodies in the late endosomes. The latter fuse with lysosomes forming a hybrid transient endolysosome to finally form secondary lysosomes. BMP is enriched in ILVs, and its levels increase during endosome maturation, contributing to ILV formation, ceramide degradation, and cholesterol efflux (45). In CLN3-deficient cells, BMP levels are decreased, potentially leading to reduced ILV formation, as well as impaired degradation and therefore accumulation of cholesterol, glycosylceramides, and glycerophosphodiesters, all contributing to lysosomal dysfunction.