Neprilysin 4: an essential peptidase with multifaceted physiological relevance.

Neprilysins are highly conserved ectoenzymes that hydrolyze and thus inactivate signaling peptides in the extracellular space. Herein, we focus on Neprilysin 4 from Drosophila melanogaster and evaluate the existing knowledge on the physiological relevance of the peptidase. Particular attention is paid to the role of the neprilysin in regulating feeding behavior and the expression of insulin-like peptides in the central nervous system. In addition, we assess the function of the peptidase in controlling the activity of the sarcoplasmic and endoplasmic reticulum Ca²⁺ ATPase in myocytes, as well as the underlying molecular mechanism in detail.