Structural biology of ferritin nanocages

Ferritin is a ubiquitous and evolutionarily conserved iron‐storage protein that plays a fundamental role in cellular iron homeostasis. By catalyzing the oxidation of ferrous iron and sequestering it as a ferric mineral within a protein nanocage, ferritin prevents toxic accumulation of labile iron and reactive oxygen species that damage proteins, lipids, and DNA. In humans, ferritin assembles into a 24‐subunit nearly spherical shell enclosing a central cavity that safely stores thousands of iron atoms. This organized architecture enables ferritin to act as both an efficient iron detoxification system and a dynamic intracellular iron reservoir. Recent advances in cryo‐electron microscopy (cryo‐EM) have transformed ferritin research by revealing its structural organization, molecular interactions, and functional states at high resolution. Additionally, beyond protein–protein interactions, cryo‐EM now enables direct visualization of ferritin‐mediated biomineralization, allowing in situ observation of iron nucleation, mineral growth, and core organization within intact nanocages. Together, these advances establish cryo‐EM as a transformative tool for elucidating ferritin structure, dynamics, and function – reshaping our understanding of iron metabolism and guiding the rational design of ferritin‐based nanomaterials for biomedical applications.