It will be important to clarify, whether internalization of SPARC is mediated by the albumin receptor gp60, which has already been shown to bind SPARC on endothelial cells, and if the chaperone function of SPARC is required for albumin transcytosis across the endothelial cell layer in normal blood vessels, which is stimulated by SPARC. In an apparent contradiction, the phenotype of SPARC knockout mice suggests abnormality in matrix deposition and Torin 1 maturation rather than impaired matrix degradation. These animals develop early-onset cataracts, profound ageprogressive osteopenia, abnormalities in collagen deposition in fragile skin, and enlarged adipose tissue. Despite significant acceleration of wound healing, scars are abnormal and collagen deposition is impaired in SPARC-null animals with cardiac infarcts, causing increased incidence of cardiac rupture and 4-times higher mortality. The issue can be resolved if proper scavenging is necessary to remove abnormalities during matrix deposition and to prevent premature termination of growing ECM networks. Indeed, unusually high rates of matrix degradation indicate that it is essential for normal ECM deposition and maturation. Most of newly synthesized collagen is immediately degraded, especially in tissues with high functional requirements. This process increases with age, reaching about a 90% ratio of degradation to synthesis in heart and muscle tissues. A lack of repair may be evident in the eye lens of SPARC-null mice, where accumulated abnormalities lead to a loss of transparency. In transgenic animals, SPARC has also been demonstrated to associate with other age- and matrix-related disorders, including periodontosis and decrease in myocardial stiffness. Essentially two mechanisms of collagen degradation are currently recognized. In the extracellular pathway, matrix is cleaved by secreted matrix metalloproteinases and cathepsin. In the intracellular pathway, collagen receptors a2b1-integrin or urokinase plasminogen activator receptor-associated protein mediate phagocytosis and lysosomal degradation of collagen in fibroblast cells. Whether SPARC is capable of connecting extra- and intracellular pathways by clearing proteolysed ECM debris, should be addressed in the future. Further studies of dynamic interactions between cells and their extracellular environment will also be required to validate the importance of scavenger chaperone in normal and pathologic physiology. It is nevertheless evident that matrix remodeling and repair is indispensable for the normal function of tissues and organs. A further understanding of SPARC’s role as a chaperone for ECM proteins will provide insight into the pathogenesis of matrix-associated disorders, and may lead to the development of novel treatment strategies. Voltage-gated potassium channels form a diverse gene family with 40 members in humans divided into 12 subfamilies. Because mutations in over sixty channel genes are already known to result in human disease, developing viable genetic models to study individual ion channel functions and channelopathies is of increasing clinical importance. KCNQ channels are a particular hotspot of genetic diseases reflecting.