Table 1.

Summary of discussed lysosomal deficiencies mediating kidney diseases.

Disease	Gene Symbol; Protein	Intracellular localization	Function	Storage material in kidney	Effect of genetic mutations on human kidney	Effect of genetic mutations on mouse kidney
Cystinosis	CTNS; Cystinosin [39]	Lysosome [76]	Cystine transporter [42]	Cystine [37]	Acquired severe proximal tubule ‘swan neck’ deformity [45, 46]	Mild tubular dysfunction in C57BL/6 ctns−/− [77]
Fabry’s	GLA;α-galactosidase [4, 28]	Lysosome[1, 28]	Enzyme[28]	GSL [31]	GSL accumulates predominantly in podocytes, mesangial cells and parietal epithelial cells leading to glomerulosclerosis, interstitial fibrosis, proteinuria and resulting in renal failure [1, 3, 27]	GSL accumulates predominantly in proximal and distal tubular epithelial cells and does not result in renal failure.[28]
Batten (JNCL)	CLN3; ceroid lipofucinosis, neuronal 3[21]	Early and late endosomes, and lysosomes; subcellular localization changes in response to osmotic stress [78]	Transmembrane protein possibly involved in membrane trafficking.	Not known	No human kidney defects have been reported.	Cln3 lacz/lacz mice on a C57BL/6J background have urine concentrating defect, polyuria and hyperkalemia[23]
Pseudo-hypoaldosteronism, type IIB	WNK4/with no lysine 4[79]	Tight junctions[79]; perinuclear and peripheral granular structures[25]	Serine/threonine Kinase[79]; maintains homeostasis of ion channels and transporters in part by regulating the targeting of NCC to lysosomes[25]	None known	Hypertension, hyperkalemia, metabolic acidosis[79]	Wnk4 D561A/+ mice develop hypertension, hyperkalemia, metabolic acidosis[80]
Action myoclonus-renal failure syndrome (AMRF)	SCARB2/LIMP2; Scavenger receptor class B, Member 2 [18]	Lysosomes and endosomes[18]	Endosome to lysosome trafficking[18]	None known	Renal failure, FSGS, Nephrotic-proteinuria[10]	Proteinuria[18], hydronephrosis[81]
Dent’s/Dent 1 [11]	CLCN5; CLC-5 [12]	Endosomes[14]	Voltage-gated chloride/proton antiporter; vesicle trafficking [14]	None known	LMW proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis and renal failure[12]	LMW proteinuria, hypercalciuria and nephrocalcinosis, [14, 82]
Oculo-Cerebro-Renal syndrome of Lowe (OCRL)/Dent 2 [11]	OCRL1; OCRL [17]	Golgi and early endosomes[17]; primary cilium [83]	Lipid phosphatase; membrane trafficking regulator[17]	None known	LMW proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis and renal failure [11]	Ocrl1−/− mice have no renal phenotype. However, ocrl1−/−; inpp5b−/− mice carrying transgenic human INPP5B locus manifest human Dent 2 renal symptoms [84].
	CD63 also known as LAMP3 or Limp1	Plasma membrane, late endosomes, lysosomes[19]	Tetraspanin likely regulates membrane trafficking [85].	Abnormal intracellular lamellar inclusions in principal cells [19]	No kidney defects have been reported.	Reduced urine osmolality, polyuria [19]
	PIK3C3; vacuolar sorting protein defective 34 (vps34) [67]	early endosomes[67]	Lipid kinase, regulates early endosomal sorting, and possibly endosome to lysosome trafficking in podocytes [67]	LAMP1 and LAMP2 positive vacuoles accumulate [68]	No kidney defects have been reported.	Conditional knock out in podocytes results in renal interstitial inflammation, fibrosis, proteinuria, renal failure [67, 68]

Abbreviations in Table 1: GSL = glycosphingolipids, FSGS= focal segmental glomerulo-sclerosis, NCC= sodium chloride co-transporter, LMW= low molecular weight.