This edited work is a constructive collaboration between experts and authorities worldwide on the biology, function, and translational medicine of the apolipoprotein E gene (APOE) polymorphisms and protein isoforms. It encompasses various aspects of innate and acquired immunology, and gastrointestinal and neurological functions, and presents the latest literature on the basic mechanisms, signaling pathways, gene editing, and novel approaches to intervention and preventive measures against disease states throughout the lifespan. In addition, this book provides an insightful discussion on the role of APOE4 in human evolution and its potential contribution to antagonistic pleiotropy, malnutrition, fertility, and enteric infections. It offers concise topics ranging from the biochemistry and biological functions of apoE to the potential pharmacological and molecular medicine strategies for disease remediation, particularly for neurodegenerative and cardiovascular diseases. This book is a constructive effort to advance our understanding of APOE4 and its effects on homeostasis and disease in various body systems.