FBXL4 and mitochondrial DNA depletion syndrome: Among the proteins recently reported as mutated in a subset of patients with mtDNA depletion syndromes is the F-box and leucine-rich repeat 4 protein (FBXL4) (Bonnen et al., 2013; Huemer et al., 2015; Almannai et al., 2017; Dai et al., 2017), an orphan member of the F-box family of proteins that are key components of the Skp1-Cullin-F-box (SCF) ubiquitin ligase complex (Bai et al., 1996), and thus, play a role in ubiquitination (Cenciarelli et al., 1999; Winston et al., 1999).