MSH2 and hereditary disease: • MSH3 is involved in double-strand break (DSB) repair via homologous recombination (Tseng-Rogenski et al. (2020) and references therein) and it seems to be a shuttling protein itself. Due to its involvement in Huntington’s disease (HD) and related human genetic diseases, the control of the subcellular localization of MutSβ (MSH2-MSH3 heterodimer) has been pursued as a novel therapeutic opportunity. Treatments that favors acetylated MutSβ allow it to exit the nucleus but hinder its nuclear reentry.