GBA is a lysosomal enzyme crucial for glycolipid metabolism, produced by the GBA gene on chromosome 1q21. Comprising three domains, it breaks down glucosylceramide into glucose and ceramide within lysosomes.

Key functions include:

• Maintaining cellular quality control
• Managing sphingolipid metabolism
• Regulating cellular processes like autophagy and inflammation

GBA mutations are linked to:

• Gaucher disease
• Increased Parkinson's disease risk (5x higher)

A critical discovery is the interaction between GBA and α-synuclein. Decreased GBA activity can cause α-synuclein aggregation, creating a detrimental feedback loop that impairs cellular functions.

The GBA-α-synuclein relationship is bidirectional:

• Reduced GBA activity leads to α-synuclein accumulation
• Accumulated α-synuclein further inhibits GBA function

Therapeutic approaches are advancing:

• Enzyme replacement therapy (ERT)
• Small molecule chaperones
• Strategies targeting GBA-α-synuclein connection

Challenges include:

• Blood-brain barrier limitations
• Variability in mutation severity
• Complex interactions between genetic and environmental factors

Ongoing research focuses on developing biomarkers and innovative treatment strategies to address GBA-related disorders.