The elevated expression of stress proteins is considered to be a universal response to adverse conditions, representing a potential mechanism of cellular defense against disease and a potential target for novel therapeutics, including gene therapy and chaperone-modulating reagents. Recently, a single mutation in the small heat-shock protein human αB-crystallin was linked to desmin-related myopathy, which is characterized by abnormal intracellular aggregates of intermediate filaments in human muscle. New findings demonstrate that the high level of expression of stress proteins can contribute to an autoimmune response and can protect proteins that contribute to disease processes.