Ndufs4 encodes a subunit of Complex I of the mitochondrial electron transport chain; mutations in the NDUFS4 gene cause LS in humans (Budde et al., 2000, 2003; Darin et al., 2001; Anderson et al., 2008; Quintana et al., 2010), and the Ndufs4 knockout (KO) mouse is a murine model of LS (Kruse et al., 2008; Quintana et al., 2010). Here, NDUFS4 is linked to Leigh syndrome.