This chapter discusses the functions of ECM, its structure, function and disorders of collagen, glycosaminoglycans (GAGs) and proteoglycans. For the proper functioning of the cell, it is important that each of its proteins must be localized to the correct organelle, such as mitochondria and lysosome. Also, the process of protein targeting, sorting and its biomedical importance are discussed here. Mislocalized proteins have been associated with human diseases. Therapeutic manipulation of protein localization in human diseases is promising.