Centrosome linker protein CEP68 modulates cellular stress responses via nuclear condensate formation and HSP27 interaction.

CEP68 is best known for its role at the centrosome linker, but its functions beyond the centrosome remain largely unexplored. Here, we show that CEP68 also localizes to the Golgi apparatus and nucleus, where it contributes to the stress response. CEP68 associates with stress response proteins, modulating eIF2α phosphorylation and stress granule (SG) formation during oxidative stress. In the nucleus, CEP68 forms liquid-like nuclear condensates adjacent to nuclear speckles (NSs), influencing their protein dynamics. The small heat shock protein HSP27, which translocates to NSs during stress, interacts with CEP68 under normal conditions, with this interaction markedly enhanced during stress. HSP27 regulates CEP68 condensate dynamics, while CEP68 nuclear condensates displace HSP27 from NSs. Both neuropathy-associated HSP27 mutants and a disease-linked CEP68 variant alter their interaction. These findings uncover a new role for CEP68 in stress response and provide insights into HSP27's functions in stress adaptation, neuropathy, and immune regulation.