N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD)

N-acyl phosphatidylethanolamine phospholipase D, or NAPE-PLD, is an enzyme that releases anandamide and related lipid messengers from a membrane precursor when a cell is stimulated.

Anandamide synthesis begins when a fatty acid is transferred onto the head group of phosphatidylethanolamine, a common membrane lipid, forming NAPE. NAPE-PLD then cuts that precursor to free anandamide directly, a step that depends on calcium and so occurs when a neuron or immune cell becomes active. The same enzyme produces palmitoylethanolamide and oleoylethanolamide, which act mainly outside the cannabinoid receptors. Because mice lacking NAPE-PLD still make some anandamide, researchers know that alternative multi-step routes exist.

The enzyme is expressed throughout the brain, in the gut and in fat, and its activity is one factor setting endocannabinoid tone. Readers meet the abbreviation in review articles that diagram the full system alongside FAAH, MAGL and DAGL. No established interaction between CBD and NAPE-PLD has been described, and the term is included for completeness.