Gamma-interferon-inducible lysosomal thiol reductase (GILT)

Gamma-interferon-inducible lysosomal thiol reductase (GILT) is a soluble lysosomal enzyme optimized for activity at acidic pH. It catalyzes the reduction of disulfide bonds in proteins inside endocytic and lysosomal compartments, crucial for the unfolding and eventual proteolysis of both self and foreign proteins. GILT plays a central role in preparing protein antigens for presentation via MHC class I and II molecules and influences central tolerance, autoimmunity, and cancer survival by modulating redox status, autophagy, and T cell activation. GILT ensures optimal activity of lysosomal cysteine proteases (such as cathepsins) by maintaining their active-site cysteines in the reduced thiol state, especially in immune cells under acidic conditions. Its expression is constitutive in antigen-presenting cells and can be induced by IFN-γ, further linking it to immune response and pathogen defense. Recent research highlights GILT’s importance for cellular redox regulation, immune system homeostasis, bone resorption, and its possible relevance in various disease states including cancer, autoimmunity, neurodegenerative and metabolic disorders

Other names

IFI30Lysosomal thiol reductaseGamma-interferon-inducible lysosomal thiol reductase (GILT)

For enzymes like GILT, a hypothetical mechanism of action would include enhancement or inhibition of disulfide bond reduction for the purposes of modulating antigen processing, immune response, or cellular redox states. Lysosomal-targeted drugs (such as enzyme replacement therapies) work by restoring specific functions of deficient lysosomal enzymes, but none are approved to specifically modulate GILT