Alteration in pH causes inhibition of lysosomal acidic proteases causing a diminished proteolysis effect. Autophagosomes then fuse with lysosomes facilitating the degradation of engulfed cargo by lysosomal proteases. Further, SRP-6 inhibits lysosomal cysteine proteases released after lysosomal rupture. Only recently have studies of human patients shown deficiency of lysosomal aspartyl proteinase cathepsin D. The production of lysosomal proteins suggests one method of lysosome sustainment. This acidic environment causes dissociation of the lysosomal enzymes from the mannose 6-phosphate receptors. It is localized in the lysosome, where it remains associated with the lysosomal membrane. Metabolic diseases such as glycogen storage disorders and lysosomal storage disorders are also implicated. NASH is also associated with lysosomal acid lipase deficiency. TFEB is a master gene for lysosomal biogenesis. Synthesis of lysosomal enzymes is controlled by nuclear genes. It resides at the intersection of the secretory, lysosomal, and endocytic pathways. Ambroxol has recently been shown to increase activity of the lysosomal enzyme glucocerebrosidase. For example, phosphorylation of oligosaccharides on lysosomal proteins occurs in the early CGN. Hunter Syndrome is caused by a deficiency of the lysosomal enzyme iduronate-2-sulfatase (I2S).