It was demonstrated that PD‐L2 acted as an upstream factor of RhoA‐ROCK‐LIMK2 and inhibited the RhoA‐ROCK‐LIMK2 signaling pathway when PD‐L2 expression was downregulated, which helped to inhibit osteosarcoma cell autophagy and this can inhibit the metastasis of osteosarcoma. The gene discussed is RHOA; the disease is osteosarcoma.