USP30 is a mitochondrial outer membrane-tethered deubiquitinase that serves as a key negative regulator of mitophagy by antagonizing parkin-mediated mitochondrial quality control 1. The enzyme preferentially cleaves Lys-6 and Lys-11-linked polyubiquitin chains, counteracting parkin's ubiquitination of mitochondrial substrates such as RHOT1/MIRO1 and TOMM20, thereby blocking mitophagy initiation 1. USP30's inhibitory role extends beyond mitochondria to peroxisomal quality control, where it regulates pexophagy through modulation of ubiquitinated PEX5 2. The protein also functions in metabolic regulation, as IKKβ-mediated phosphorylation stabilizes USP30, which then deubiquitinates ATP citrate lyase (ACLY) and fatty acid synthase, promoting lipogenesis and contributing to hepatocellular carcinoma development 3. Therapeutically, USP30 represents a promising target for neurodegenerative diseases, particularly Parkinson's disease, where its inhibition can rescue defective mitophagy in parkin-deficient neurons and reduce oxidative stress 4. USP30 inhibition also shows potential in treating metabolic cardiomyopathies by restoring mitophagy in fatty acid oxidation-deficient hearts 5 and enhancing cancer immunotherapy by preventing T cell exhaustion through improved mitochondrial quality control 6.