Persons with 2 high-risk alleles in APOL1, the gene encoding apolipoprotein L1, are at increased risk of kidney disease. Genetic and environmental modifiers likely contribute substantially to an individual’s risk. The lifetime risk of developing kidney failure among persons with high-risk APOL1 genotypes, defined by the presence of 2 of the G1 or G2 coding variants, is ∼15%.1 Recent work has identified an intragenic modifier variant in APOL1, M1 (p.N264K), which, when co-inherited with the G2 risk allele, appears to provide a protective effect on the risk of kidney disease.