The fact that other F-box proteins could regulate important cardiac pathways, such as Fbxo33 [regulation of growth factors by YB-1 (Lutz et al., 2006; Lyabin et al., 2014)], Fbxo45 [regulator of p73 and mTOR signalling (Peschiaroli et al., 2009; Saiga et al., 2009; Han et al., 2012; Chung et al., 2014)], Ddb1 [associated with hypertension phenotype in a specific population with a polymorphism that impairs the function of Gβ3 to target GRK2 ubiquitination (Zha et al., 2016)] opens exciting new insights that should be investigated in the future. The gene discussed is YBX1; the disease is Hypertension.