The pyrin inflammasome senses OCTN2-mediated uptake of extracellular ʟ-carnitine from muscle injury or ingestion

ʟ-Carnitine is a nonproteinogenic amino acid highly abundant in myocytes, and both excess ingestion of myocytes and myocyte necrosis are associated with systemic inflammation. Here, we find that the pyrin inflammasome senses extracellular ʟ-carnitine through the high-affinity carnitine transporter OCTN2 (SLC22A5) and this leads to IL-1β-mediated inflammation. Our findings position OCTN2 as a potential target to reduce inflammation from exogenous or endogenous sources of extracellular ʟ-carnitine.