TABLE 2.
Genes responsible for HSP encoding proteins modifying cellular lipid metabolism.
| Gene | Protein name | Function |
| Lipid droplets (LD) | ||
| ATL (SPG3) | Atlastin | Regulation of LD size |
| SPAST (SPG4) | Spastin | Regulation of LD size and number |
| REEP1 (SPG31) | REEP1 | Regulation of LD size |
| CPT1C (SPG73) | Carnitine palmitoyl transferase 1C | Regulation of LD size and number |
| Spartin (SPG20) | Spartin | Regulation of LD size and number |
| DDHD2 (SPG54) | DDHD2 | Triacylglycerol lipase, hydrolysis of LD |
| Mitochondrial function | ||
| DDHD1 (SPG28) | DDHD1 | Mitochondria fusion/fission, ROS production, ATP synthesis |
| DDHD2 (SPG54) | DDHD2 | Mitochondria fusion/fission, ROS production, ATP synthesis, regulate levels of cardiolipins |
| SERAC1 | SERAC1 | Altered levels of cardiolipins, altered function of the respiratory chain |
| Spartin (SPG20) | Spartin | Regulation of mitochondrial membrane potential |
| ABCD1 (X-ALD) | Adrenoleukodystrophy protein (ADLP) | Mitochondrial depolarization, ROS production |
| Lysosome function | ||
| GALC (Krabbe) | Galactosylcerebrosidase | Accumulation of psychosine |
| ARSA (MLD) | Arylsulfatase A | Accumulation of sulfatides |
| ATP13A2 (SPG78) | P5-type ATPase | Regulates lysosomal degradative activity, accumulation of membranes in lysosomes |
| AP5Z1 (SPG48) | Subunit ζ of adapter complex 5 | Accumulation of membranes in lysosomes |
| SPG11 | Spatacsin | Regulation of autophagic lysosome recovery, accumulation of gangliosides in lysosomes |
| ZFYVE26 (SPG15) | Spastizin | Regulation of autophagic lysosome recovery, accumulation of membranes in lysosomes |
| SERAC1 | SERAC1 | Reduced levels of bis-monoacylglycerol-phosphate in lysosomes |
| Synaptic function | ||
| PLA2G6 | Group VI phospholipase A2, iPLA2b | Alteration of synaptic structure |
| PNPLA6/NTE (SPG39) | Patatin-like phospholipase domain containing 6/Neuropathy target esterase | Reduction of the activity of the secretory pathway |
| BSCL2 (SPG17) | Seipin (N88S variant: altered glycosylation of seipin) | Decreased number of docked synaptic vesicles in sypases |
| Myelin/axon maintenance | ||
| PLP1 (SPG2) | Proteolipid protein | Constituent of myelin, required for long term axon maintenance |
| MAG (SPG75) | Myelin associated glycoprotein | Constituent of myelin, binds to gangliosides present in axon membrane, required for long term axon maintenance |
| GJC2 (SPG44) | Connexin 47 | Gap junction protein, required for glial coupling in white matter |
| FA2H (SPG35) | Fatty acid-2 hydroxylase | Decreased levels of galactosylceramide, required for long-term axon maintenance |
| GALC (Krabbe) | Galactosylcerebrosidase | Defective myelin formation and later on demyelination; psychosine-induced toxicity of oligodendrocytes |
| ARSA (MLD) | Arylsulfatase A | Demyelination |