Uyama_2025_Int.J.Mol.Sci_26_

N-Acylethanolamines (NAEs) are a class of lipid mediators that consist of long-chain fatty acids condensed with ethanolamine and exert various biological activities depending on their fatty acyl groups. NAEs are biosynthesized from membrane phospholipids by two-step reactions or alternative multi-step reactions. In the first reaction, N-acyltransferases transfer an acyl chain from the sn-1 position of phospholipids to the amino group (N position) of phosphatidylethanolamine (PE), generating N-acyl-PE (NAPE), a precursor of NAE. So far, two types of N-acyltransferases have been identified with different levels of Ca(2+)-dependency: cytosolic phospholipase A(2) sigma (cPLA(2)sigma) as a Ca(2+)-dependent N-acyltransferase and phospholipase A and acyltransferase (PLAAT) enzymes as Ca(2+)-independent N-acyltransferases. Recent in vivo studies using knockout mice with cPLA(2)sigma and PLAAT enzymes, combined with lipidomic approaches, have clarified their roles in the skin and brain and in other physiological events. In this review, we summarize the current understanding of the functions and properties of these enzymes.