Trim21 is an E3 ubiquitin ligase that prepares proteins for proteasomal and lysosomal degradation.36 Our recent work demonstrated that the Trim21/ANXA2/TFEB axis is critical for the regulation of OB differentiation via autophagy in osteosarcoma.19 In the present study, unbiased screening of Trim21-deficient mouse BMSCs revealed that YAP1, by cooperation with BCL9/β-catenin signaling, is crucial for Trim21-regulated bone remodeling (Fig. 4 and Fig. 6). Here, TRIM21 is linked to osteosarcoma.