Table 1.

HSP proteins involved in the endolysosomal system and autophagy. The cellular consequences mentioned here are only in the context of this review, and therefore only include the function of the protein in the endolysosomal and autophagic pathways. All the references to the SPG numbers and their clinical involvement can be found in Hedera et al. or Boutry et al. [11,12].

SPG	Gene	Protein	Relevant Section in the Text	Contribution in the Pathway	Cellular Consequences of Mutation/Depletion	References
SPG3A	ATL1	Atlastin-1	2.2 Receptor trafficking 2.3 Secretory pathway	Regulation of BMP signaling ER-Golgi trafficking	Overactivation of BMP signaling Impairment of ER-Golgi trafficking and Golgi morphogenesis	[26,27,28,29]
SPG4	SPAST	Spastin	2.1 Endocytosis and endosomes’ dynamic 2.2 Receptor trafficking	Regulation of ESCRT-III	Perturbation of endosomal tubulation Overactivation of BMP signaling	[30,31,32,33,34]
SPG6	NIPA1	NIPA1	2.2 Receptor trafficking	Regulation of BMP signaling	Overactivation of BMP signaling	[28,35,36]
SPG8	KIAA0196/ WASHC5	Strumpellin/ WASHC5	2.1 Endocytosis and endosomes’ dynamic 2.2 Receptor trafficking	Member of WASH complex	Perturbation of clathrin-independent pathway Impairment of endosomal tubulation	[23,24,25]
SPG10	KIF5	KIF5A	3.2 Autophagosome—lysosome fusion	Kinesin, motor protein	Impairment of the axonal transport and autophagic flux	[37]
SPG11	SPG11	Spatacsin	3.3 Lysosome membrane recycling	Recruitment of Dynamin Interacts with spastizin and AP-5	Autophagy defects due to reduction of autolysosome tubulation Accumulation of autophagic compartments Defective lysosomal clearance of gangliosides	[16,38,39,40,41]
SPG15	ZFYVE26	Spastizin	3.3 Lysosome membrane recycling 3.4 Crossroads between endocytic and autophagic pathways	Interacts with spatacsin and AP-5 Interaction with Rab5A and Rab11	Autophagy defects due to reduction of autolysosome tubulation Accumulation of autophagic compartments Altered maturation of autophagosomes	[38,39,40,42,43]
SPG20	SPART	Spartin	2.1 Endocytosis and endosomes’ dynamic 2.2 Receptor trafficking	Regulation of ESCRT-III	Perturbation of endosomal trafficking Overactivation of BMP signaling	[44,45,46,47,48,49]
SPG30	KIF1A	KIF1A/Unc-104	3.1 Autophagosome biogenesis	Kinesin, motor protein	Impaired transport of ATG-9-positive vesicles leading to defects in autophagosome biogenesis	[50]
SPG39	PNPLA6	PNPLA6	2.2 Receptor trafficking	Regulation of BMP signaling	Overactivation of BMP signaling	[51]
SPG42	SLC33A1	SLC33A1	2.2 Receptor trafficking	Regulation of BMP signaling	Overactivation of BMP signaling	[52]
SPG47	AP4B1	AP4B1	2.3 Secretory pathway 3.1 Autophagosome biogenesis 3.3 Lysosome membrane recycling	Subunit of AP-4 complex	Impairment of ATG9A’s sorting and thus autophagosome biogenesis	[53,54,55]
SPG48	AP5Z1	AP5Z1	3.3 Lysosome membrane recycling 3.4 Crossroads between endocytic and autophagic pathways	AP-5 subunit spatacsin and spastizin interactor	Reduction of autolysosome tubulation Impaired endolysosomal system due to accumulation of endolysosomes Impairment of CIMPR trafficking towards TGN	[56,57,58,59]
SPG49	TECPR2	TECPR2	3.2 Autophagosome—lysosome fusion	Interactor of HOPS and ATG8 family members	Accumulation of autophagosomes due to impaired autophagosome—lysosome fusion	[60,61]
SPG50	AP4M1	AP4M1	2.3 Secretory pathway 3.1 Autophagosome biogenesis 3.3 Lysosome membrane recycling	Subunit of AP-4 complex	Impairment of ATG9A’s sorting and thus autophagosome biogenesis	[53,54,55]
SPG51	AP4E1	AP4E1	2.3 Secretory pathway 3.1 Autophagosome biogenesis 3.3 Lysosome membrane recycling	Subunit of AP-4 complex	Impairment of ATG9A’s sorting and thus autophagosome biogenesis	[53,54,55]
SPG52	AP4S1	AP4S1	2.3 Secretory pathway 3.1 Autophagosome biogenesis 3.3 Lysosome membrane recycling	Subunit of AP-4 complex	Impairment of ATG9A’s sorting and thus autophagosome biogenesis	[53,54,55]
SPG53	VPS37A	VPS37A	2.1 Endocytosis and endosomes’ dynamic 3.1 Autophagosome biogenesis	Subunit of ESCRT-I	Perturbation of endosomal sorting Altered capacity to recruit ESCRT-I subunits at the PAS leading to impaired autophagosome closure	[62,63]
SPG58	KIF1C	KIF1C	2.3 Secretory pathway	Kinesin, motor protein	Impairment of Golgi-ER transport	[64,65,66]
SPG69	RAB3GAP2	Rab3GAP2	3.4 Crossroads between endocytic and autophagic pathways	Subunit of Rab3GAP complex	Autophagy defects	[67,68]
SPG78	ATP13A2/ PARK9	ATP13A2	3.2 Autophagosome—lysosome fusion	Still unclear	Autophagy defects due to accumulation of autophagic compartments	[69,70]
SPG80	UBAP1	UBAP1	2.1 Endocytosis and endosomes’ dynamic	Subunit of ESCRT-I	Perturbation of endosomal sorting	[71,72]
\	VCP	VCP	2.1 Endocytosis and endosomes’ dynamic 3.4 Crossroads between endocytic and autophagic pathways	Interaction with strumpellin Autophagosome maturation	Perturbation of strumpellin localization and function Autophagy defects	[73,74,75,76]
\	VPS53	VPS53	2.3 Secretory pathway	Subunit of GARP complex	Still unclear	[77]