RHBDF2 and intracranial hemorrhage: Homozygous Rhbdf1 knockout mice (KO) exhibit multiorgan pathologies, including brain hemorrhage, cardiac fibrosis, and lower body weight compared with heterozygous littermates, and die within two weeks after birth (Christova et al. 2013; Hosur et al. 2020) (Fig. 2A). Conversely, Rhbdf2-null mice are healthy and fertile and do not present with growth retardation or brain and heart defects (Hosur et al. 2014; Adrain et al. 2012; McIlwain et al. 2012; Siggs et al. 2012) (Fig. 2B).