LYST (lysosomal trafficking regulator) is an adapter protein that regulates intracellular vesicle trafficking, particularly the fusion and fission of lysosomes and lysosome-related organelles 1. In cytotoxic T cells and natural killer cells, LYST controls the size, number, and exocytosis of lytic granules, critical for immune cytotoxicity 2. LYST also regulates phagosome maturation in macrophages and dendritic cells, and modulates TLR3/TLR4-induced inflammatory responses by controlling endosomal signaling pathways 2. Additionally, LYST plays a prominent role in autophagosome-lysosome reformation for lysosomal homeostasis maintenance 2. Mutations in LYST cause Chediak-Higashi syndrome (CHS), a rare autosomal recessive immunodeficiency characterized by congenital immunodeficiency, partial oculocutaneous albinism, bleeding diathesis, and progressive neurodegeneration 23. Mutation type correlates with disease severity: nonsense/frameshift mutations cause classic CHS with severe early-onset immunodeficiency and high hemophagocytic lymphohistiocytosis (HLH) risk, while missense mutations cause milder immunologic symptoms but inevitable neurological progression 3. LYST mutations also contribute to broader HLH disease spectrum, with degranulation defects including LYST variants representing >50% of genetic HLH cases 4. Hematopoietic stem cell transplantation effectively treats hematologic and immune defects but does not prevent progressive neurological complications 2.