Our findings reveal that during sepsis, TLR4 serves as the primary receptor for eCIRP and plays a crucial role in mediating its internalization in ECs as shown in Fig. 3, although some other receptors, such as triggering receptor expressed on myeloid cells-1 and interleukin-6 receptor have been previously identified as eCIRP receptors and serve different roles under various physiological and pathological conditions [8, 9, 41]. Here, IL6R is linked to Sepsis.