Updated project metadata. SUMMARY Congenital muscular dystrophy with laminin á2 chain-deficiency (MDC1A) is one of the most severe forms of muscular disease and is characterized by decreased muscle tone at birth, reduced movements and contractures. The genetic basis of MDC1A is well-known, yet the secondary mechanisms ultimately leading to muscle degeneration and subsequent connective tissue infiltration are not fully understood. In order to obtain new insights into the molecular mechanisms underlying MDC1A, we performed a comparative proteomic analysis of affected muscles (diaphragm and gastrocnemius) from laminin á2 chain-deficient dy3K/dy3K mice, using the multidimensional protein identification technology combined with tandem mass tags. Out of the around 700 identified proteins, 113 and 101 proteins, respectively, were differentially expressed in the diseased gastrocnemius and diaphragm muscles compared to normal muscles. A large portion of these proteins are involved in different metabolic processes, bind calcium or are expressed in the extracellular matrix. Our findings suggest that metabolic alterations and calcium dysregulation could be novel mechanisms that underlie MDC1A and might be targets that should be explored for therapy. Also, detailed knowledge of the composition of fibrotic tissue, rich in extracellular matrix proteins, in laminin á2 chain-deficient muscle may help to design future anti-fibrotic treatment.