DDHD2's Role in Supplying Saturated Fats for Brain Energy and Function

The study reveals that DDHD2 enzyme releases saturated fatty acids like myristic, palmitic, and stearic acids, which fuel mitochondrial beta-oxidation to support neuronal energy production. Loss of DDHD2 impairs this pathway, leading to reduced ATP, mitochondrial dysfunction, and neurological deficits akin to hereditary spastic paraplegia. Supplementing with CoA-conjugated fatty acids restores mitochondrial function and may offer a therapeutic approach for HSP54.