These changes may underlie IBMPFD pathogenesis.24,25 ATPase activity of p97 is essential in maintaining CCND1, a critical regulator of the RB1/E2F1 pathway, and inhibition of p97 promotes the degradation of CCND1.58 Our data showed that the treatments with either an ATP-competitor or allosteric p97 inhibitor, CB-5083 and NMS-873 respectively, relieves phenotypes in p97R155H/+ MNs, including reducing cell death and reducing changes in markers linked to disease pathology (NES, p53 and γ-H2Ax). Here, RB1 is linked to inclusion body myopathy with Paget disease of bone and frontotemporal dementia.