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Purpose of Review <p>Apolipoprotein A-I (APOA1) is the primary protein and structural scaffold on high density lipoproteins (HDL), playing key roles in HDL biogenesis, reverse cholesterol transport (RCT), regulation of systemic lipid metabolism, and cardiovascular protection. This review aims to trace the lifecycle of APOA1, from its cellular synthesis to its contributions in HDL formation, remodeling and eventual clearance or recycling through the body. By highlighting APOA1’s structural versatility, we focus on how its transitional states enable functional adaptation at various stages of its metabolic journey.</p> Recent Findings <p>Advancements in structural biology highlight how APOA1’s conformations drive its interactions with lipid transporters, enzymes, and cellular receptors. These transitions regulate HDL biogenesis and remodeling, with evidence suggesting APOA1’s early lipid-free state may serve as a critical determinant of its role on mature HDL particles. New studies also explore underexplored pathways, such as APOA1’s potential contributions to immune modulation and journey in the lymphatics system.</p> Summary <p>With its dynamic structural properties, APOA1 remains essential for HDL metabolic adaptation, systemic lipid transport, and inflammatory protection. Despite recent years of progress, key gaps remain, including elucidating structural conformations on lipid surfaces, their role in particle remodeling, and their relevance to metabolic fate. Addressing these areas through advanced imaging techniques and structural workflows in human-relevant models could provide therapeutic opportunities to enhance APOA1 function and combat cardiovascular and other metabolic diseases.</p>

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The Structural and Functional Journey of Apolipoprotein A-I Through the Human Body

  • 期刊论文

  • 发表日期：

    2026年4月21日

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  • Samantha M. Powell,
  • Youngki You,
  • Chinemerem P. Ogbu,
  • John T. Melchior

摘要

Purpose of Review

Apolipoprotein A-I (APOA1) is the primary protein and structural scaffold on high density lipoproteins (HDL), playing key roles in HDL biogenesis, reverse cholesterol transport (RCT), regulation of systemic lipid metabolism, and cardiovascular protection. This review aims to trace the lifecycle of APOA1, from its cellular synthesis to its contributions in HDL formation, remodeling and eventual clearance or recycling through the body. By highlighting APOA1’s structural versatility, we focus on how its transitional states enable functional adaptation at various stages of its metabolic journey.

Recent Findings

Advancements in structural biology highlight how APOA1’s conformations drive its interactions with lipid transporters, enzymes, and cellular receptors. These transitions regulate HDL biogenesis and remodeling, with evidence suggesting APOA1’s early lipid-free state may serve as a critical determinant of its role on mature HDL particles. New studies also explore underexplored pathways, such as APOA1’s potential contributions to immune modulation and journey in the lymphatics system.

Summary

With its dynamic structural properties, APOA1 remains essential for HDL metabolic adaptation, systemic lipid transport, and inflammatory protection. Despite recent years of progress, key gaps remain, including elucidating structural conformations on lipid surfaces, their role in particle remodeling, and their relevance to metabolic fate. Addressing these areas through advanced imaging techniques and structural workflows in human-relevant models could provide therapeutic opportunities to enhance APOA1 function and combat cardiovascular and other metabolic diseases.