The first substrate of SENP5 identified was the tumor suppressor PML, which has an essential role in the regulation of cell proliferation [146], and SENP5 function has been associated with cytokinesis and the safeguard of mitochondria functionality; the latter being related to cytoplasmic desumoylation of DRP1 protein by SENP5, which inhibits mitochondria fragmentation [147,148]. The gene discussed is SENP5; the disease is neoplasm.