S-acylation of TDP-43: PALMing down aggregation?

S-acylation is well known for regulating protein stability and trafficking. In a recent issue of Molecular Cell, Xu et al.1 reveal a distinct, aggregation-suppressing function of this posttranslational lipid modification: S-acylation of the RNA-binding protein TDP-43 antagonizes poly(ADP-ribose)-driven condensation. Moreover, reduced S-acylation levels are linked to ALS pathogenesis.