Lysosomal-trafficking regulator

LYST (Lysosomal-trafficking regulator) is an adapter protein that regulates intracellular vesicle dynamics, particularly lysosomal fission and trafficking. It plays critical roles in cytotoxic T-cell and natural killer cell granule exocytosis, phagosome maturation in macrophages and dendritic cells, and TLR3/TLR4-induced inflammatory signaling through endosomal pathways (UniProt: Q99698).

Mutations in LYST cause Chediak-Higashi syndrome, a severe autosomal recessive disorder affecting lysosomal transport and immune function (UniProt: Q99698). The protein's broad involvement in vesicular trafficking and immune regulation positions it within pathways relevant to neuroinflammation and cellular homeostasis.

LYST is downregulated in Alzheimer's disease brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.56 across a single subcellular fraction in TMT-labeled post-mortem proteomics (Chaparral AD proteomics). This reduction may reflect impaired lysosomal dynamics and vesicular trafficking in AD pathology, though the modest magnitude and single-fraction measurement warrant further investigation across additional AD cohorts and brain compartments.