2.4.2. NEDD4-2 and Pendrin

Although there is limited information available regarding the role of UPS in the intercalated cells (ICs) of CNT and CD, a recent study has demonstrated a role of NEDD4-2 in regulating electrolyte transport mechanisms in these cells [67]. Nanami et al. examined the phenotype of IC-specific NEDD4-2 knockout mice and found that these mice displayed increased pendrin abundance and Cl−/HCO3 − transport in the ICs, accompanied by the elevation of BP [67]. Furthermore, pendrin gene ablation was found to eliminate the BP increase observed in global NEDD4-2 knockout mice. These data indicate that the ubiquitin ligase NEDD4-2 in ICs is also involved in electrolyte transport and regulation of BP.

### **3. Role of UPS in the Regulation of Vascular Function**
