Persons with two 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 two 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.