PRKN encodes parkin, an E3 ubiquitin ligase that plays a critical role in mitochondrial quality control and cellular homeostasis. The protein functions within the PINK1-PRKN pathway to regulate mitophagy, the selective degradation of damaged or dysfunctional mitochondria 12. Upon mitochondrial damage, PINK1 phosphorylation activates PRKN, which then ubiquitinates mitochondrial proteins including VDAC1, TOMM20, and MFN1/MFN2 to promote mitophagy 31. PRKN catalyzes various types of ubiquitination (K6, K11, K48, K63-linked) depending on cellular context and substrate requirements 4. Beyond mitophagy, PRKN protects cells from inflammatory responses triggered by mitochondrial damage-associated molecular patterns, as demonstrated in PRKN knockout mice showing enhanced inflammation following exhaustive exercise 5. The protein also regulates cellular senescence and oxidative stress responses, with PRKN deficiency leading to accumulation of damaged mitochondria and accelerated aging in disease models 6. Mutations in PRKN cause early-onset Parkinson's disease, highlighting its critical role in neuronal survival 7. Therapeutically, compounds that enhance PRKN-mediated mitophagy show promise for neurodegenerative diseases, while PRKN dysregulation contributes to cancer cell survival under metabolic stress 8.