Fig. 7

Erbin rescues sepsis-induced ALP dysfunction by binding to TFEB, alleviating inflammation response and organ injuries. In this model, the NOD2-NF-κB pathway is activated on DAMPs and PARMs stimulation, resulting in the dysfunction of ALP, especially the disrupted lysosomal acidic environment. In this process, Erbin physically interacts with TFEB and regulates TFEB-14-3-3 and TFEB-PPP3BC complexes stability, which regulates the TFEB nuclear translocation, thus regulating TFEB transcription levels and improving lysosomal biogenesis. Thus, impaired Erbin-mediated ALP leads to an aggravated sepsis inflammation response and a deteriorated prognosis. Those suggested that Erbin's targeting of TFEB might rescue the dysfunctional ALP and alleviate the inflammation response and organ injuries following sepsis