GCase deficiency in PD-linked GBA1 mutations leads to progressive glucosylceramide (GlcCer) accumulation in lysosomal membranes, fundamentally altering their biophysical properties. GlcCer preferentially localizes to ordered lipid domains (lipid rafts), which are precisely the membrane microdomains required for SNX5 (sorting nexin 5) association with the retromer complex. SNX5 serves as a critical bridge between the VPS35-VPS29-VPS26 trimer and phosphoinositide-specific membranes, mediating the
Radar Chart — 10 Dimensions
Score Comparison Bars
Mechanistic
0.78
Evidence
0.78
Novelty
0.72
Feasibility
0.75
Impact
0.76
Druggability
0.00
Safety
0.00
Competition
0.00
Data
0.00
Reproducible
0.55
KG Connect
0.19
Score Breakdown
Dimension
Glucosylceramide Accumulation
Mechanistic
0.780
Evidence
0.780
Novelty
0.720
Feasibility
0.750
Impact
0.760
Druggability
0.000
Safety
0.000
Competition
0.000
Data
0.000
Reproducible
0.550
KG Connect
0.187
Evidence
Glucosylceramide Accumulation from GCase Deficiency Disrupts