Intracellular lysosomal soluble proteins

Intracellular lysosomal soluble proteins represent a diverse group of approximately 60 acid hydrolases, including proteases, glycosidases, and lipases, that reside within the lysosomal lumen [1] (Nature Reviews Molecular Cell Biology). These proteins are essential for the degradation and recycling of macromolecules such as proteins, lipids, and nucleic acids, thereby maintaining cellular homeostasis and facilitating autophagy [2] (Nature Reviews Disease Primers). Deficiencies in these soluble enzymes lead to lysosomal storage diseases (LSDs), characterized by the toxic accumulation of undigested substrates in various tissues [2]. Beyond LSDs, these proteins are implicated in the progression of cancer and neurodegenerative disorders like Parkinson's disease [4] (Molecular Genetics and Metabolism). In therapeutic contexts, these proteins are the targets of enzyme replacement therapies (ERT), where recombinant versions of the enzymes are administered to patients [4]. Furthermore, emerging technologies like Lysosome-Targeting Chimeras (LYTACs) utilize these proteins to facilitate the degradation of extracellular and membrane-bound pathogenic targets [3] (Nature).

Other names

Lysosomal hydrolasesAcid hydrolasesLysosomal lumenal proteinsLysosomal enzymes

Enzyme replacement therapy (ERT) provides exogenous functional enzymes to compensate for deficiencies; pharmacological chaperones stabilize misfolded enzymes; and Lysosome-Targeting Chimeras (LYTACs) recruit these proteins to degrade extracellular targets.