It has been reported that in BMP/TGF-β signaling, BMP4 binds its receptor and signals to activate the downstream transcription factor SMAD4, leading to the transcription of PPARγ and facilitating of adipogenesis.44,45 Our study reveals that ANXA1 reduces SMAD4 protein accumulation through protein-protein interactions (PPIs), inhibits PPARγ transcription, and ameliorates obesity and metabolic disorders (Fig. 7k). Here, SMAD4 is linked to metabolic disease.