It is demonstrated that megalin-mediated endocytosis involves the uptake of lipid-toxic glomerular-filtered substances, affecting the function of the endosome/lysosome system and resulting in autophagy impairment, followed by the increased production of profibrotic and inflammatory mediators in PTECs, which activates interstitial fibrocytes/pericytes to induce renal fibrosis (Kuwahara et al., 2016). This evidence concerns the gene LRP2 and renal fibrosis.