The fhl1 gene encoding four and half LIM protein (FHL1) and its spliced isoform, SLIMMER is mutated in reducing body myopathy, XMPMA, scapuloperoneal myopathy and rigid spine syndrome. In this study we have identified a novel function for SLIMMER, in delaying skeletal muscle apoptosis via an interaction with the pro-apoptotic protein Siva-1. Siva-1 was identified as a SLIMMER-specific interacting protein using yeast two-hybrid screening, direct binding studies and GST-pull down analysis of murine skeletal muscle lysates. In C2C12 skeletal myoblasts SLIMMER and Siva co-localized in the nucleus, however both proteins exhibited redistribution to the cytoplasm following the differentiation of mononucleated myoblasts to multinucleated myotubes. In sections of mature skeletal muscle from wild type mice SLIMMER and Siva-1 co-localized at the Z-line. SLIMMER and Siva-1 were also enriched in Pax-7-positive satellite cells, muscle stem cells which facilitate repair and regeneration. Significantly, SLIMMER delayed Siva-1-dependent apoptosis in C2C12 myoblasts. In skeletal muscle sections from the mdx mouse model of Duchenne muscular dystrophy, SLIMMER and Siva-1 co-localized in the nucleus of apoptotic myofibres. Therefore, SLIMMER may protect skeletal muscle from apoptosis.