Notably, PARL’s significant role in maintaining mitochondrial fitness has been established through critical studies that identified its substrates, such as PINK1 (Jin et al., 2010), a mitochondrial kinase implicated in Parkinson’s disease and mitophagy (Valente et al., 2004; Yan et al., 2020), PGAM5 (Sekine et al., 2012), a mitochondrial phosphatase implicated in Parkinsonism in mice (Lu et al., 2014), and TTC19 (Saita et al., 2017), a mitochondrial protein involved in maintaining complex III activity and associated with human Leigh syndrome (Bottani et al., 2017; Atwal, 2014). The gene discussed is PINK1; the disease is Parkinson disease.