Lysosomal proteins

Lysosomal proteins encompass a broad class of enzymes, transporters, and structural proteins essential for the function of lysosomes, the cell's primary degradative and recycling centers [1, 12]. These proteins, including over 60 acid hydrolases and numerous membrane-bound transporters, facilitate the breakdown of macromolecules like proteins, lipids, and polysaccharides into their basic components [14, 15]. Beyond degradation, they are integral to nutrient sensing and metabolic regulation, particularly through the recruitment and activation of the mTORC1 complex on the lysosomal membrane [2, 13]. Genetic mutations in these proteins lead to lysosomal storage disorders (LSDs), such as Gaucher and Fabry disease, where the accumulation of undegraded substrates causes systemic organ damage [3, 19]. Lysosomal dysfunction is also a hallmark of neurodegenerative diseases like Parkinson's and Alzheimer's, as well as cancer, where lysosomes support tumor growth and survival [4, 24]. Therapeutic interventions targeting these proteins include enzyme replacement therapies, pharmacological chaperones, and substrate reduction agents [20, 21]. Emerging strategies also explore lysosome-targeted protein degradation and the inhibition of lysosomal acidification to treat malignancies and autoimmune conditions [18, 25].

Other names

Lysosomal enzymesLysosomal membrane proteinsAcid hydrolasesLysosomal transportersLysosomal ion channelsLMPs

Enzyme replacement therapy (ERT) to restore catalytic activity; pharmacological chaperone therapy (PCT) to stabilize misfolded proteins; substrate reduction therapy (SRT) to decrease metabolite accumulation; inhibition of lysosomal acidification to disrupt autophagic flux in cancer; and modulation of lysosomal signaling hubs like mTORC1.