In ADPKD, Obermuller et al. observed that loss of chloride channel CIC-5 and the albumin receptor megalin led to proteinuria in ADPKD (cy/+) rats, and the impairment in endocytosis could further reduce the efficacy of certain gene therapy (Obermuller et al., 2001; Witzgall et al., 2002). The gene discussed is LRP2; the disease is autosomal dominant polycystic kidney disease.