that were more severe in cardiac relative to skeletal muscle. Cardiac tissue also exhibited progressive necrosis and calcification of the myocardium. A separate study examined this in more detail in cardiac tissue and found that murine hearts lacking desmin developed hypertrophic cardiomyopathy and chamber dilation combined with systolic dysfunction. In adult muscle, desmin forms a scaffold around the Z-disk of the sarcomere and connects the Z-disk to the subsarcolemmal cytoskeleton. It links the myofibrils laterally by connecting the Z-disks. Through its connection to the sarcomere, desmin connects the contractile apparatus to the cell nucleus, mitochondria, and post-synaptic areas of motor endplates. These connections maintain the structural and mechanical integrity of the cell during contraction while also helping in force transmission and longitudinal load bearing. In human heart failure, desmin expression is upregulated, which has been hypothesized to be a defense mechanism in an attempt to maintain normal sarcomere alignment amidst disease pathogenesis. There is some evidence that desmin may also connect the sarcomere to the extracellular matrix (ECM) through desmosomes which could be important in signalling between the ECM and the sarcomere which could regulate muscle contraction and movement. Finally, desmin may be important in mitochondria function. When desmin is not functioning properly there is improper mitochondrial distribution, number, morphology and function. Since desmin links the mitochondria to the sarcomere it may transmit information about contractions and energy need and through this regulate the aerobic respiration rate of the muscle cell. Clinical significance Desmin-related myofibrillar myopathy (DRM or desminopathy) is a subgroup of the myofibrillar myopathy diseases and is the result of a mutation in the gene that codes for desmin which by changing the protein structure prevents it from forming protein filaments, and rather, forms aggregates of desmin and other proteins throughout the cell. Desmin (DES) mutations have been associated with restrictive, dilated, idiopathic, arrhythmogenic and non-compaction cardimyopathy. The N-terminal part of the 1A desmin subdomain is a genetic hot spot region for mutations affecting filament assembly. Some of these DES mutations cause an aggregation of desmin within the cytoplasm. A mutation p.A120D was discovered in a family, where several members had sudden cardiac death. In addition, DES mutations cause frequently cardiac conduction diseases. Desmin has been evaluated for role in assessing the depth of invasion of urothelial carcinoma in TURBT specimens. References External links GeneReviews/NIH/NCBI/UW entry on Myofibrillar Myopathy LOVD mutation database: DES Tumor markers