Phosphatidylethanolamine: Structural Component and Beyond

Phosphatidylethanolamine (PE) is a major phospholipid in biological membranes and plays essential roles in autophagy, cell signaling, protein function, and membrane integrity. Its dynamic, conical structure supports membrane fluidity and curvature, which are crucial for processes such as signaling, autophagosome formation, membrane fusion, vesicle trafficking, and proper protein folding. Although PE is abundant, its significance for human health and disease has only recently come to light. Altered PE levels or disruptions in its metabolism have been associated with various conditions, including metabolic disorders such as non-alcoholic fatty liver disease (NAFLD), neurodegenerative diseases like Alzheimer's and Parkinson's, and several cancers. PE is synthesized primarily via two pathways: the CDP-ethanolamine (Kennedy) pathway and the mitochondrial phosphatidylserine decarboxylase (PSD) pathway, both of which are critical for maintaining lipid homeostasis. Advances in lipidomics now allow comprehensive profiling of PE species, facilitating the identification of disease-specific lipid biomarkers. This review expands current knowledge on the physiological roles of PE and elucidates mechanisms underlying PErelated lipid dysregulation in human disease.