Human ferritins are expressed in essentially all cells of the human body. From an evolutionary perspective, human ferritins are part of a diverse ferritin-like superfamily—the ‘rubrerythins’, that include plant ferritins and bacterioferritins, where they cover a wide range of biological functions.1 Although best known as a 24-meric intracellular iron storage protein, ferritin is also present in the human circulation, where its biological functions are still being unravelled. Recent studies have shown that ferritin can be actively secreted from cells in extracellular vesicles (EVs). These ferritin-laden EVs can contribute to the pathogenesis of liver steatosis and fibrogenesis by shuttling iron from hepatocytes to hepatic stellate cells.2 Hence, in patients with metabolic syndrome, serum ferritin is more than a surrogate of body iron status.3 Especially in metabolic dysfunction-associated steatotic liver disease (MASLD), which is the now preferred term for a disease that has until recently been known as non-alcoholic fatty liver disease (NAFLD), serum ferritin is strongly correlated with liver fibrosis and disease progression.4 5

Inflammation is a hallmark of progressive MASLD and liver inflammation is a key feature of metabolic dysfunction-associated steatohepatitis (MASH). Although underlying mechanisms responsible for initiation of inflammation in MASLD remain somewhat unclear, it is increasingly accepted that various hits such as lipotoxicity, endoplasmic reticulum stress, insulin resistance or gut dysbiosis contribute to liver and/or systemic inflammation.6 Gut-derived bacterial components such as endotoxin might especially play …