Deconjugating enzymes (DCEs) are proteases that process ubiquitin or ubiquitin-like gene products, reverse the modification of proteins by a single ubiquitin or ubiquitin-like protein (UBL) and remodel polyubiquitin (or poly-UBL) chains on target proteins (Reyes-Turcu et al., 2009). The deubiquitylating - or deubiquitinating - enzymes (DUBs) represent the largest family of DCEs and regulate ubiquitin dependent signalling pathways. The activities of the DUBs include the generation of free ubiquitin from precursor molecules, the recycling of ubiquitin following substrate degradation to maintain cellular ubiquitin homeostasis and the removal of ubiquitin or ubiquitin-like proteins (UBL) modifications through chain editing to rescue proteins from proteasomal degradation or to influence cell signalling events (Komander et al., 2009). There are two main classes of DUB, cysteine proteases and metalloproteases. Ubiquitin specific protease 30 (USP30) is a member of the cysteine protease enzyme family and cloning of the gene was first described by Quesada et al. (2004). USP30 can be found anchored to the mitochondrial outer-membrane (MOM), contributing to the regulatory mechanism for mitochondrial dynamics in mammalian cells. A loss of USP30 activity has been shown to disturb the maintenance of mitochondrial morphology and lead to mitochondrial elongation (Nakamura and Hirose, 2008). Loss-of-function mutations in PINK1 kinase and the ubiquitin E3 ligase Parkin, are a significant cause of early onset Parkinson's disease. PINK1 activates Parkin to induce selective autophagy of damaged mitochondria. After recruitment, Parkin mediates the engulfment of mitochondria by autophagosomes and the selective elimination of impaired mitochondria. Parkin promotes autophagy of damaged mitochondria and implicates a failure to eliminate dysfunctional mitochondria in the pathogenesis of Parkinson's disease (Kane et al., 2014; Narendra et al., 2008). A small molecule inhibitor of USP30 has recently been identified and reported. The diterpenoid derivative is a natural molecule named 15-oxospiramilactone (S3) that induces mitochondrial fusion to restore the mitochondrial network and oxidative respiration in cells that are deficient in mitochondrial fusion genes mitofusin 1 (Mfn1) or mitofusin 2 (Mfn2). The inhibition of USP30 by S3 leads to an increase of Mfn1/2 activity promoting mitochondrial fusion (Yue et al., 2014).