Edward P.K. Kwakyi, BSc, and Rasheed A. Gbadegesin, MBBS, MD, FASN, discuss the role of apolipoprotein L1 (APOL1) in kidney diseases, particularly in people of African ancestry. APOL1 is a major driver of chronic kidney disease (CKD) in this population, but more research is needed to understand its exact impact. They also discuss the higher prevalence of APOL1-associated kidney disease in African Americans compared with West Africans, suggesting that factors such as mortality rates, modifier genes, and environmental disease modifiers could be responsible. Dr Gbadegesin advocates for routine screening for APOL1 high-risk genes in at-risk populations, but notes that more understanding is needed about why some people develop APOL1-mediated kidney disease and others do not. They also discuss promising new treatments for APOL1-mediated kidney disease, emphasizing the need for diverse clinical trials.