Sachini Thanthirige

This study presents the first crystal structure of the Ubiquilin Sti1 domain bound to a transmembrane domain, showing that ALS mutations disrupt their interaction and reveal internal placeholder sequences that regulate phase separation.

This study shows UBQLN2 stabilizes substrates by recruiting E3 ligases, which promotes phase separation and protects against proteasomal degradation, and this mechanism is disrupted in ALS mutants.