NDUFS4 and Leigh syndrome: Additionally, the NDUFS4 knockout mouse (ndufs4−/−) is one of the most widely used mouse models for investigating the pathomechanism of LS, a rare, complicated, and incurable early-onset pediatric disorder with both phenotypic and genetic heterogeneity featuring brain-specific anomalies (Quintana et al., 2010, 2012; Grillo et al., 2021).