LIAT1 (ligand of ATE1) is a regulatory protein that functions as a cofactor in the N-end rule protein degradation pathway and participates in nucleolar organization. Mechanistically, LIAT1 interacts with arginyl-tRNA protein transferase 1 (ATE1) to stimulate N-terminal arginylation of protein substrates 1, a post-translational modification that targets proteins for proteasomal degradation. Additionally, LIAT1 functions as an RNA-binding protein capable of binding arginyl-tRNA, suggesting roles in coordinating protein and tRNA metabolism 2. LIAT1's N-terminal intrinsically disordered region (IDR) mediates liquid-liquid phase separation (LLPS) in the nucleolus, where it forms dynamic membraneless condensates 3. This nucleolar targeting is regulated by the lysyl-hydroxylase Jmjd6, which modifies LIAT1 through its poly-K region to inhibit nucleolar localization 3. Disease relevance extends to neurodegenerative diseases, as LIAT1-mediated ATE1 signaling regulates TDP-43 proteostasis, with TDP-43 dysfunction implicated in ALS and frontotemporal dementia 2. The evolutionary conservation of LIAT1 across vertebrates and primates, including variable 10-residue tandem repeats in primate lineages, suggests conserved physiological importance 1.