Prkn, also known as parkin RBR E3 ubiquitin protein ligase, is a crucial gene involved in protein ubiquitination and mitophagy of damaged mitochondria. It is a key component of the PINK1-PRKN pathway, which is essential for mitochondrial quality control. Mitophagy, the selective elimination of dysfunctional mitochondria, is vital for maintaining cellular homeostasis, and Prkn's role in this process underscores its biological importance. Genetic models, such as knockout (KO) mouse models, have been instrumental in studying Prkn [1-10].

In COPD research, prkn KO mice showed enhanced airway wall thickening with emphysematous changes after cigarette smoke exposure. Their airway epithelial cells had accumulated damaged mitochondria, increased oxidative modifications, and accelerated cellular senescence. In vitro, PRKN overexpression could induce mitophagy even with reduced PINK1 levels, while PINK1 overexpression couldn't rescue mitophagy impairment caused by PRKN knockdown, indicating PRKN is a rate-limiting factor in the PINK1-PRKN-mediated mitophagy during cigarette smoke extract exposure. This suggests that PRKN levels are pivotal in COPD pathogenesis [1]. In triple-negative breast cancer, hypoxia-induced GPCPD1 depalmitoylation regulated PRKN-mediated ubiquitination of VDAC1 to trigger mitophagy, and GPCPD1-mediated mitophagy promoted tumor growth and metastasis [2]. In Parkinson's disease, homozygous or compound heterozygous loss-of-function variants in PRKN are common, and PRKN-linked familial Parkinson's disease results from various mechanisms of gene variant-induced loss-of-function [3].

In conclusion, Prkn is essential for mitochondrial quality control through its role in mitophagy. The use of Prkn KO mouse models has provided valuable insights into its role in diseases like COPD, triple-negative breast cancer, and Parkinson's disease. Understanding Prkn's function helps to elucidate the mechanisms of these diseases and may potentially lead to the development of novel therapeutic strategies.