NDUFS4 is an 18 kDa accessory subunit that assembles the catalytic N-module (where NADH oxidation occurs) with the rest of the complex I. Mutations leading to the loss of NDUFS4 result in complex I deficiency (Zhu et al., 2016; Stroud et al., 2016; Gu et al., 2016; Kahlhöfer et al., 2017; Scacco et al., 2003) and are involved in cardiomyopathies, both in protective (ischemia/reperfusion injury) and detrimental roles (pressure overload) (Chouchani et al., 2014; Karamanlidis et al., 2013; Zhang et al., 2018). Here, NDUFS4 is linked to cardiomyopathy.