Apolipoprotein L1 (APOL1) (APOL1)

Apolipoprotein L1 (APOL1) is a primate-specific protein that circulates in the blood as part of high-density lipoprotein (HDL) particles and is also expressed locally in tissues such as the kidney, liver, and vascular endothelium [11, 12]. Its primary biological function is to provide innate immunity against Trypanosoma brucei parasites by forming ion-conducting pores in the parasite's lysosomal membrane, leading to osmotic swelling and lysis [10, 15]. However, specific genetic variants (G1 and G2), which are prevalent in individuals of African ancestry, are strongly associated with a spectrum of chronic kidney diseases, including focal segmental glomerulosclerosis (FSGS) and HIV-associated nephropathy [1, 2]. These variants exhibit a toxic gain-of-function by forming active cation channels in the plasma membrane of podocytes, resulting in ion imbalances (such as potassium efflux and calcium influx) that trigger cell stress and death [3, 14]. Therapeutic strategies are currently focused on small molecule inhibitors, such as inaxaplin, which directly target and block the APOL1 pore's conductance to prevent cellular injury and slow the progression of kidney disease [4, 6].

Other names

ApoL1FSGS4Apolipoprotein L-1Trypanosome lytic factor

Small molecule inhibition of APOL1 channel function; reduction of APOL1 protein synthesis via antisense oligonucleotides or siRNA