Emerging concepts in the molecular cell biology and functions of mammalian erythrocytes

Erythrocytes, or red blood cells, are essential components of vertebrate blood, comprising approximately 45% of human blood volume. Their distinctive features, including small size, biconcave shape, extended lifespan (∼115 days), and lack of a nucleus or other membrane-bound organelles, make them unique among mammalian cell types. Traditionally regarded as passive carriers of oxygen and carbon dioxide, erythrocytes were long thought to function merely as hemoglobin-filled sacs, incapable of gene expression or roles beyond gas transport. However, advancements in molecular biology have revealed a more complex picture. Recent studies have identified various RNA types within erythrocytes, demonstrated globin mRNA translation, and uncovered miRNA-mediated defenses against Plasmodium infection. Beyond gas exchange, erythrocytes play critical roles in regulating regional blood flow via nitric oxide, contribute to innate immunity through toll-like receptors, transport amino acids between tissues, and maintain water homeostasis. Furthermore, emerging technologies have repurposed erythrocytes as drug-delivery vehicles, opening new avenues for therapeutic applications. This review highlights these recent discoveries and explores the expanding functional landscape of erythrocytes, shedding light on their multifaceted roles in physiology and medicine.