LAUSR

Mucopolysaccharidoses (MPS) are a group of 13 diseases (see Table 1 for details) belonging to lysosomal storage disorders (LSD) that occur with cumulative frequencies of all their types of about 1 per 40,000—50,000 live births (Çelik et al., 2021). Out of these 13 types of MPS, 11 are known since many years, while 2 types were discovered recently, MPS X (Verheyen et al., 2022) and MPS-plussyndrome (MPSPS) (Vasilev et al., 2020). All MPS diseases are caused by mutations in genes coding for enzymes involved in metabolism (usually catabolism) of glycosaminoglycans (GAGs) (formerly called mucopolysaccharides). Their impaired hydrolysis or other stage(s) of metabolism leads to continuous accumulation and storage of these compounds in cells of patients which results in a damage of the affected tissues, including the heart, respiratory system, bones, joints, and central nervous system (Fecarotta et al., 2020). MPS are usually fatal diseases (especially neuronopathic forms of MPS), with average expected life span less than 2 decades (or significantly shorter in some cases). MPS are monogenic diseases, which are often considered model genetic diseases in studies on mechanisms of genetic disorders and development of novel therapeutic strategies (Tomatsu et al., 2018). Although MPS are monogenic diseases, recent studies demonstrated that their pathomechanisms are significantly more complex than primary effects of GAG storage on lysosomal functions. It appeared that expression of hundreds of genes is changed inMPS cells (Gaffke et al., 2020). This causes further changes in proteome (De Pasquale et al., 2020a) and metabolome (De Pasquale et al., 2020b), and resultant disturbances of structures and functions of cellular organelles and many cellular processes (Gaffke et al., 2021), finally leading to dysfunctions of tissues, organs, and the whole body. Nevertheless, our knowledge on the molecular processes occurring in MPS cells, and disease-specific changes relative to normal cells, is still limited. On the other hand, understanding molecular pathomechanisms of the disease, especially molecular aspects of various interactions between biologically active macromolecules, is crucial for both gaining basic knowledge on regulation of various biological processes and developing new therapeutical strategies for genetic diseases which are particularly difficult to cure. In fact, previous studies on MPS allowed to achieve spectacular progress in understanding principles of genetic disorders and to propose many sophisticated therapeutical options, including enzyme replacement therapy, substrate reduction therapy, modifications of gene therapies, and many others (McBride and Flanigan 2021). Interestingly, studies on MPS provided a basis for intriguing proposals concerning diseases from other groups, including unexpected aspects of COVID-19 (Pierzynowska et al., 2020; De Pasquale et al., 2021). Therefore, a special issue of this journal has been devoted to present papers which can increase our knowledge on the molecular aspects of MPS. This should provide broader view on these diseases, indicate possible novel tools for their analyses, and have significantly broader meaning for bio-medical sciences. Edited and reviewed by: Cecilia Giulivi, University of California, Davis, United States