The Ndufs4 knockout (KO) mouse model of LS (JAX, 2017; Kruse et al., 2008) has become an essential tool for investigating the tissue-specific consequences of mitochondrial CI deficiency with most research focused on the brain and the vulnerability of neurons to CI deficiency (van de Wal et al., 2022). Here, NDUFS4 is linked to hyperinsulinemic hypoglycemia, familial, 4.