LTO1 (LTO1 maturation factor of ABCE1) is a conserved protein essential for iron-sulfur cluster maturation and ribosome biogenesis. As part of the LTO1:YAE1 complex, LTO1 functions as a target-specific adapter that recruits the apo-ABCE1 protein to the cytosolic iron-sulfur protein assembly (CIA) machinery for iron-sulfur cluster insertion 1. LTO1 is required for large ribosomal subunit (60S) maturation and translation initiation, with its function being particularly critical under aerobic conditions where reactive oxygen species (ROS) pose threats to ribosomal integrity 2. Mechanism: LTO1 works in complex with YAE1 and ABCE1 to protect ribosomes from oxidative damage while facilitating iron-sulfur cluster assembly. The complex relieves toxic effects of ROS on ribosome biogenesis and function 2. Disease relevance: LTO1 is frequently overexpressed in solid tumors, including head and neck squamous cell carcinoma, myeloma, breast, lung, and pancreatic cancers 3. Recently, the LTO1/YAE1 complex was identified as a regulator of nonsense-mediated RNA decay (NMD), which controls major histocompatibility complex class I (MHC-I) expression in tumor cells 4. Clinical significance: LTO1 deficiency impairs NMD and enhances MHC-I expression, increasing T cell activation and tumor recognition 4. Iron chelators that inhibit NMD through LTO1 pathway modulation show promise for enhancing cancer immunotherapy efficacy 4.