In this report, we found that the K7 of Rab22a-NeoF1, acetylated by p300/CBP while de-acetylated by both HDAC6 and SIRT1, plays a key role in its binding to SmgGDS607, and consequently affects its activation of RhoA and promotion of cell migration, invasion and lung metastasis in osteosarcoma. Here, RAB22A is linked to osteosarcoma.