Apolipoprotein L1 and mechanisms of kidney disease susceptibility

Curr Opin Nephrol Hypertens. 2021 May 1;30(3):317-323. doi: 10.1097/MNH.0000000000000704.


Purpose of review: Allelic variants in the gene for apolipoprotein L1 (APOL1), found only in individuals of African ancestry, explain a majority of the excess risk of kidney disease in African Americans. However, a clear understanding how the disease-associated APOL1 variants cause kidney injury and the identity of environmental stressors that trigger the injury process have not been determined.

Recent findings: Basic mechanistic studies of APOL1 biochemistry and cell biology, bolstered by new antibody reagents and inducible pluripotent stem cell-derived cell systems, have focused on the cytotoxic effect of the risk variants when APOL1 gene expression is induced. Since the APOL1 variants evolved to alter a key protein-protein interaction with the trypanosome serum resistance-associated protein, additional studies have begun to address differences in APOL1 interactions with other proteins expressed in podocytes, including new observations that APOL1 variants may alter podocyte cytoskeleton dynamics.

Summary: A unified mechanism of pathogenesis for the various APOL1 nephropathies still remains unclear and controversial. As ongoing studies have consistently implicated the pathogenic gain-of-function effects of the variant proteins, novel therapeutic development inhibiting the synthesis or function of APOL1 proteins is moving toward clinical trials.

Trial registration: ClinicalTrials.gov NCT04340362 NCT04269031.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Apolipoprotein L1* / genetics
  • Disease Susceptibility
  • Genetic Predisposition to Disease
  • Humans
  • Kidney Diseases* / genetics
  • Kidney Diseases* / therapy
  • Podocytes


  • APOL1 protein, human
  • Apolipoprotein L1

Associated data

  • ClinicalTrials.gov/NCT04340362
  • ClinicalTrials.gov/NCT04269031