Osteosarcoma is highly heterogeneous, and its pathogenesis remains unclear.Increasing research indicates that E3 ubiquitin ligases play a significant role in the onset, invasion, metastasis, and targeting of osteosarcoma.Firstly, regarding the occurrence of osteosarcoma, M6A RNA methylation plays a crucial role in regulating the growth and progression of osteosarcoma cells, controlling tumor development through the regulation of USP22/RNF40 and histone ubiquitination (Yadav et al., 2022). The gene discussed is PRKN; the disease is osteosarcoma.