In this issue of Clinical Science , Schueller et al. [Clin. Sci. (2017) 131, 1971-1987] evaluated the role of miR-223 across multiple etiologies of acute and chronic liver insults in murine models and clinical samples. The authors find that while miR-223 is not mechanistically involved in liver injury, its intracellular levels in hepatocytes are increased upon hepatic damage in a broad panel of mechanistically distinct injury models. Furthermore, the authors provide evidence that circulating miR-223 levels provide a promising minimally invasive biomarker for acute liver failure (ALF) that defines a distinct subset of ALF cases and correlates with clinical outcomes. Combined, the highlighted study suggests that miR-223 constitutes a promising biomarker whose clinical validity and utility warrant further investigations.