Tsr1, also known as pre-rRNA-processing protein TSR1 homolog, is involved in ribosome biogenesis, specifically in the cytoplasmic steps of 40S subunit maturation [4]. Structurally, it has a domain architecture similar to translational GTPases but lacks the active site residues for GTP binding and hydrolysis [4]. It may also play a role in the MAPK-Erk signaling pathway in addition to ribosome assembly [3].

In a study on a Chinese congenital cataract family, a novel TSR1 mutation was identified. The TSR1 c.202-1G>A substitution affected splicing of TSR1 mRNA. Expression of Tsr1 was detected in mouse and human lenses, and its down-regulation in lens-specific CBP:p300 double-knockout mouse led to the identification of six proteins interacting with Tsr1 through protein-protein interaction network analysis [3]. In another study, tRF-Gln-CTG-026 ameliorated liver injury by repressing global protein synthesis through the weakened association between TSR1 and pre-40S ribosome [1]. Additionally, TSR1 variants were associated with spontaneous coronary artery dissection (SCAD) in the Chinese Han population. Four genes were identified to have a suggestive association with SCAD, with TSR1 being the top hit. TSR1 germline variants were either highly conserved or led to premature termination of protein syntheses, and TSR1 expression was detectable in human coronary artery tissues [2].

In conclusion, Tsr1 is essential for ribosome biogenesis and may have additional functions in signaling pathways. Studies using gene-modified mouse models and human genetic analysis have revealed its potential roles in congenital cataract, liver injury, and SCAD, providing valuable insights into the molecular mechanisms underlying these diseases and potential therapeutic targets.