Polymorphisms in the gene for apolipoprotein L1 (APOL1) contribute significant risk to several forms of nondiabetic kidney disease, including focal segmental glomerulosclerosis (FSGS), severe lupus nephritis, hypertension-attributed chronic kidney disease (CKD), and HIV-associated nephropathy. The complete pathogenic mechanism behind these APOL1 nephropathies remains unclear, although several pathogenic effects have been ascribed to APOL1 variants, involving the role of interferons, intracellular ion fluxes, mitochondrial injury, endosomal trafficking defects, and cytotoxicity.