To further investigate the secretion process of SIRT1, we overexpressed FLAG-tagged WT and DEL forms of SIRT1 in HEK293 cells. SIRT1-interacting proteins were isolated from HEK293 cell extracts through co-immunoprecipitation (co-IP) using an anti-FLAG antibody. After collecting the interacting proteins through acidic elution, the samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Among the proteins showing reduced levels in the DEL group, six were associated with intracellular trafficking, secretion, and vesicular transport. The intensity of the 6 proteins that interact with DEL or WT SIRT1 were represented on a heatmap (Figure 2A). Of these, only Syntaxin-binding protein 1 (STXBP1), a peripheral membrane protein, plays a crucial role in protein secretion.