We hypothesize that mutations in HSPG2, CELA1, and KCNK5 participate in extracellular matrix modifications, arterial media remodeling, and regulation of vascular tone, all these events leading to interstitial vessel remodeling, connected to renal interstitial fibrosis in BEN (Figure 4). Here, KCNK5 is linked to Balkan nephropathy.