APOL1 is found in vascular endothelium, liver, heart, lung, placenta,[7] podocytes, proximal tubules, and arterial cells.

It forms a complex, known as a trypanosome lytic factor (TLF),[12] with high-density lipoprotein 3 (HDL3) particles that also contain apolipoprotein A1 (APOA1) and the hemoglobin-binding, haptoglobin-related protein (HPR).

If the endosome is then recycled to the plasma membrane, where it encounters neutral pH conditions, APOL1 may form cation-selective channels.

Pro-inflammatory cytokines interferon-γ(IFN), tumor necrosis factor-α (TNF-α) and p53 can increase the expression of APOL1.

[14] APOL1 has a role in innate immunity by protecting against Trypanosoma brucei infection, which is a parasite transmitted by the tsetse fly.

[5][15] Although its intracellular function has not been elucidated, apoL1 circulating in plasma has the ability to kill the trypanosome Trypanosoma brucei that causes sleeping sickness.

Recently, two coding sequence variants in APOL1 have been shown to associate with kidney disease in a recessive fashion while at the same time conferring resistance against Trypanosoma brucei rhodesiense.

[16] This resistance is due, in part, to decreased binding of the G1 and G2 APOL1 variants to the T. b. rhodesiense virulence factor, serum resistance-associated protein (SRA) as a result of the C-terminal polymorphisms.

The distribution of the variants most associated with kidney disease risk was analyzed in African populations and found to be more prevalent in western compared to northeastern African populations and absent in Ethiopia,[18] consistent with the reported protection from forms of kidney disease known to be associated with the APOL1 variants.

The prevalence of the risk alleles in African Americans with these kidney diseases shown in recent studies are 67% in HIVAN, 66% in FSGS, and 47% in hypertension-attributed ESKD.

[21][22] Hispanic populations such as Dominicans and Puerto Ricans demonstrate a mixture of genetic influences that include African ancestry resulting in a prevalence of the APOL1 variants as well.