Though antiretroviral therapies have markedly reduced the burden of HIVAN in HIV-positive patients, studies to elucidate how HIV increases susceptibility to kidney disease in persons with high risk APOL1 genotypes promise to provide key insights that may help develop novel strategies for the prevention and treatment of APOL1 nephropathies in HIV-negative patients. The gene discussed is APOL1; the disease is HIV-associated nephropathy.