The lysosome, an organelle central to macromolecule degradation and recycling, plays a pivotal role in normal cell processes, ranging from autophagy to redox regulation. Not surprisingly, lysosomes are an integral part of the renal epithelial molecular machinery that facilitates normal renal physiology. Two inherited diseases that manifest as kidney dysfunction are
Fabry's disease and
cystinosis, each of which is caused by a primary biochemical defect at the lysosome resulting from loss-of-function mutations in genes that encode
lysosomal proteins. The functions of the lysosomes in the kidney and how lysosomal dysfunction might contribute to
Fabry's disease and
cystinosis are discussed. Unlike most other pediatric renal diseases,
therapies are available for
Fabry's disease and
cystinosis, but require early diagnosis. Recent analysis of
ceroid neuronal lipofuscinosis type 3 (Cln3) null mice, a mouse model of lysosomal disease that is primarily associated with neurological deficits, revealed renal functional abnormalities. As current and future
therapeutics increase the life-span of those suffering from diseases like
neuronal ceroid lipofuscinosis, it remains a distinct possibility that many more lysosomal disorders that primarily manifest as infant and juvenile
neurodegenerative diseases may also include renal disease phenotypes.