Biosynthesis of neuroprotectin D1 [NPD1]. A membrane phospholipid containing a docosahexaenoyl chain at sn-2 is hydrolyzed by phospholipase A2, generating free (unesterified) docosahexaenoic acid [DHA] (22:6). Lipoxygenation (Calandria et al., 2009) is then followed by epoxidation and hydrolysis to generate NPD1. Thus far, a binding site for NPD1 has been identified in retinal pigment epithelial cells and polymorphonuclear cells. Modified, with permission, from the Annual Review of Nutrition, Volume 31© 2011 by Annual Reviews www.annualreviews.org