Physiologically, depletion of SPOP could increase the cellular proliferation and migration, which could be partly reversed by additional depletion of HDAC6. These findings provide the molecular insights into how loss of SPOP function may be mechanistically linked with elevated HDAC6 protein levels that may facilitate tumorigenesis and metastasis in cancer patients with SPOP-mutant genetic status. The gene discussed is HDAC6; the disease is cancer.