Synemin is a type IV intermediate filament (IF) protein that associates with of desmin and keratin IFs, costameric proteins, and alpha‐actinin in Z‐disks. It is also an A‐kinase anchoring protein (AKAP). Here, we report that genetic ablation of synemin in mice results in abnormalities in bone, skeletal, and cardiac muscle. We found osteopenia with reduction in trabecular and cortical bone fraction associated with changes in osteoblast proliferation and differentiation. Skeletal muscle in null mice have a mild phenotype denoted by decreased fiber size and force production, and increased sarcolemmal deformability and susceptibility to injury. In the heart, the absence of synemin causes left ventricular systolic dysfunction associated with hypertrophy and dilatation, and alterations in calcium handling in isolated cardiomyocytes. Thus, synmein plays important roles bone and striated muscles.Support or Funding InformationSupported partially by APS‐Physiological Genomics Fellowship and UNAM‐PAPIIT (IA 207818) to KPGP; NIH to JPS (R01‐AR063631), AMB (F31‐AR064673), CWW (R01 AR062554), WJL (R01 HL105239, U01 HL116321) and RJB (R01 AR 055928).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.