Phosphatidylethanolamine (PE) is the second most abundant phospholipid in mammals. The majority of PE is synthesized by two distinct pathways: the CDP-ethanolamine branch of the Kennedy pathway and decarboxylation of phosphatidylserine (PS) by the enzyme PS decarboxylase (PSD) located in the mitochondria. The PSD pathway is required to maintain mitochondrial structure and function and essential for life. Selathurai et al. studied the PSD pathway in muscle and found that it is important for PE synthesis in skeletal muscle and is required for maintenance of mitochondrial integrity and muscle mass. This reveals the role of mitochondria in maintaining skeletal muscle homeostasis.