SIX1 and pachyonychia congenita: In summary, this study identifies a SIX1 degradation inducer that potently inhibits CRPC cell proliferation via targeting the USP1-SIX1 axis and triggering apoptosis of PC cells in vitro and in vivo, and further provides a novel strategy with the combination of enzalutamide and the SIX1 degradation inducer for overcoming the progression of castration resistance during PC treatment (Fig. 6F).