Human apolipoprotein L1 (ApoL1) in cancer and chronic kidney disease

Human apolipoprotein L1 (ApoL1) possesses both extra- and intra-cellular functions crucial in host defense and cellular homeostatic mechanisms. Alterations in ApoL1 function due to genetic, environmental, and lifestyle factors have been associated with African sleeping sickness, atherosclerosis, lipid disorders, obesity, schizophrenia, cancer, and chronic kidney disease (CKD). Importantly, two alleles of APOL1 carrying three coding-sequence variants have been linked to CKD, particularly in Sub-Saharan Africans and African Americans. Intracellularly, elevated ApoL1 can induce autophagy and autophagy-associated cell death, which may be critical in the maintenance of cellular homeostasis in the kidney. Similarly, ApoL1 may protect kidney cells against renal cell carcinoma (RCC). We summarize the role of ApoL1 in RCC and CKD, highlighting the critical function of ApoL1 in autophagy.

► Elevated expression of ApoL1 induces autophagy, lysosomal swelling, and cell death.
► The G1 and G2 alleles of APOL1 are associated with CKD in people of African ancestry.
► Human APOL1 is expressed in kidney tubular epithelial cells and podocytes.
► Expression of ApoL1 is inducible by inflammatory cytokines (IFN, TNF) and p53.
► Extracellularly, ApoL1 binds ApoA1 in lipoprotein complexes and can function as TLF.