APOL1 nephropathy occurs in a minority of genetically at-risk individuals, suggesting that other factors, such as other genes or environmental factors, contribute. Divers and colleagues report that among individuals with two APOL1 risk alleles, those with JC viruria are less likely to manifest kidney disease compared with those lacking JC viruria. These data might suggest that JC virus infection confers protection against glomerular injury, perhaps by altering cell function or generating immunity against a related polyomavirus.