Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SN), leading to motor symptoms such as rigidity, bradykinesia, postural instability, and tremor. While most PD cases are idiopathic, autosomal dominant and recessive familial forms have been identified. PINK1 and Parkin, two genes mutated in autosomal recessive parkinsonism, play critical roles in mitochondrial quality control. PINK1 accumulates on damaged mitochondria, activates Parkin's E3 ubiquitin ligase activity, and recruits Parkin to the dysfunctional mitochondria. Parkin then ubiquitinates outer mitochondrial membrane proteins to trigger selective autophagy (mitophagy), removing damaged mitochondria and preventing neuronal death. This process is essential for maintaining mitochondrial function and preventing PD. PINK1 detects mitochondrial damage through selective proteolysis, allowing it to accumulate on dysfunctional mitochondria and activate Parkin. Parkin, in turn, ubiquitinates mitochondrial proteins, which are then targeted for degradation. The interplay between PINK1 and Parkin ensures mitochondrial fidelity and prevents the accumulation of dysfunctional mitochondria, which is a key factor in PD pathogenesis. Mutations in PINK1 or Parkin impair this process, leading to mitochondrial dysfunction and neuronal death. Understanding the molecular mechanisms of PINK1 and Parkin in mitochondrial quality control provides insights into the etiology of PD and potential therapeutic strategies.Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SN), leading to motor symptoms such as rigidity, bradykinesia, postural instability, and tremor. While most PD cases are idiopathic, autosomal dominant and recessive familial forms have been identified. PINK1 and Parkin, two genes mutated in autosomal recessive parkinsonism, play critical roles in mitochondrial quality control. PINK1 accumulates on damaged mitochondria, activates Parkin's E3 ubiquitin ligase activity, and recruits Parkin to the dysfunctional mitochondria. Parkin then ubiquitinates outer mitochondrial membrane proteins to trigger selective autophagy (mitophagy), removing damaged mitochondria and preventing neuronal death. This process is essential for maintaining mitochondrial function and preventing PD. PINK1 detects mitochondrial damage through selective proteolysis, allowing it to accumulate on dysfunctional mitochondria and activate Parkin. Parkin, in turn, ubiquitinates mitochondrial proteins, which are then targeted for degradation. The interplay between PINK1 and Parkin ensures mitochondrial fidelity and prevents the accumulation of dysfunctional mitochondria, which is a key factor in PD pathogenesis. Mutations in PINK1 or Parkin impair this process, leading to mitochondrial dysfunction and neuronal death. Understanding the molecular mechanisms of PINK1 and Parkin in mitochondrial quality control provides insights into the etiology of PD and potential therapeutic strategies.