Red Blood Cells Beyond Oxygen Transport: Dynamic Regulators, Disease Biomarkers and Therapeutic Platforms—A Narrative Review

Red blood cells (RBCs) have traditionally been regarded as passive carriers of respiratory gases. Increasing evidence, however, indicates that they are active participants in vascular homeostasis and respond to mechanical, metabolic, and oxidative stimuli. This narrative review examines the interconnected roles of RBCs as regulators of vascular physiology, indicators of hereditary and systemic disease, therapeutic targets, and delivery platforms. RBC deformability, membrane organization, ion-water balance, metabolism, and redox capacity support microcirculatory flow, while ATP release, nitric oxide handling, adhesion, and extracellular-vesicle formation influence vascular function. RBC morphology, mechanics, hydration, metabolism, oxidative status, and vesiculation can provide clinically relevant information, although emerging functional and molecular biomarkers require further standardization and validation. RBC-directed treatments and RBC-based carriers offer additional therapeutic opportunities. Automated image analysis and machine-learning-assisted microfluidic classification are the most substantiated artificial-intelligence applications; broader multimodal decision-support systems remain exploratory.