New ideas about mechanism in APOL1 kidney disease.

Apolipoprotein L1 risk variants contribute to high rates of kidney disease among individuals of African ancestry. These gain-of-function variants cause toxicity to kidney cells, but the mechanism of injury is not clear. Many theories have been proposed, yet the field has not arrived at a consensus. Kim et al. make a compelling argument for a peroxisomal pathway of injury specifically activated under hypoxic conditions. Introducing cellular context reframes the debate about apolipoprotein L1 mechanism of disease.