Mutant Cullin causes cardiovascular compromise

Mendelian hypertension is rare; however, Mendelian syndromes have taught us an amazing amount about mechanisms of distal sodium and chloride reabsorption, as well as how systemic hypertension might come about. In this issue of EMBO Molecular Medicine , Schumacher et al ([Schumacher FR, 2015]) present a mouse model of the Cullin‐3 ( CUL 3Δ403–459) mutation, which causes a form of pseudohypoaldosteronism type‐2 ( PHA ‐2). CUL 3 is involved in ubiquitination. Surprising is the severity of the hypertension, which may be explained in part on the basis of CUL 3 actions in vascular cells. The findings underscore the role of “cleanup” in the maintenance of normal physiology.