CBX4 and neoplasm: Interestingly, while most OS‐related RING E3 ubiquitin ligases have been reported to be upregulated in tumor tissues and enhance OS development, TRIM58 and RNF180 were found to be downregulated in human OS and inhibit OS progression through ubiquitination of pyruvate kinase M2 and chromobox homolog 4, respectively [29, 30].