The apolipoprotein L1 (APOL1) high-risk genotypes (G1/G1, G2/G2, and G1/G2) are among the strongest genetic risk factors for kidney disease in individuals of African ancestry, conferring a 7- to 30-fold increased risk of kidney disease.1 Despite approximately 13% of African Americans carrying these high-risk genotypes, only 15%-20% ultimately develop chronic kidney disease (CKD), whereas more than 80% maintain normal kidney function throughout their lives.2 This incomplete penetrance remains a major challenge in translating APOL1 genetics into clinical practice.