Previously, a significant overexpression of alpha‐2‐macroglobulin gene (A2M) in a glucocorticoid‐induced rat model of ANFH has been reported,10 and in a recent study, it has been shown that the serum protein level of this protein interestingly raised in ANFH patients.11 This protein has several roles in fibrinolysis and the coagulation cascade.12 Besides, it is a carrier of diverse growth factors and cytokines contributing to osteogenesis.13, 14, 15, 16 It is feasible that ACTH influences the osteogenesis and vascularization via influencing the gene expression of A2M as a role player in ANFH. Here, A2M is linked to familial avascular necrosis of femoral head.