Apolipoprotein L1 is a protein that in humans is encoded by the APOL1 gene. Two transcript variants encoding two different isoforms have been found for this gene. Species distribution This gene is found only in humans, African green monkeys, and gorillas. Structure The gene that encodes the APOL1 protein is 14,522 base pairs long and found on the human chromosome 22, on the long arm at position 13.1 from base pair 36,253,070 to base pair 36,267,530. The protein is a 398 amino acid protein. It consists of 5 functional domains: S domain-secretory signal MAD (membrane-addressing domain)-ph sensor and regulator of cell death BH3 domain - associated with programmed cell death PFD (pore forming domain) SRA (serum resistance-associated binding domain)- confers resistance to Trypanosoma brucei Mutations Two coding variants, G1 and G2, have been recently identified with relevance to human phenotypes. The G1 is a pair of two non-synonymous single nucleotide polymorphisms (SNPs) in almost complete linkage disequilibrium. G2 is an in-frame deletion of the two amino acid residues, N388 and Y389. Function Apolipoprotein L1 (apoL1) is a minor apoprotein component of HDL cholesterol) which is synthesized in the liver and also in many other tissues, including pancreas, kidney, and brain. APOL1 is found in vascular endothelium, liver, heart, lung, placenta, podocytes, proximal tubules, and arterial cells. The protein as a secreted form that allows it to circulate in the blood. It forms a complex, known as a trypanosome lytic factor (TLF), with high-density lipoprotein 3 (HDL3) particles that also contain apolipoprotein A1 (APOA1) and the hemoglobin-binding, haptoglobin-related protein (HPR). The APOL1 protein acts as the main lytic component in this complex. Once uptaken by the trypanosome, the complex is trafficked to acidic endosomes, where the APOL1 protein may insert into the endosomal membrane. If the endosome is then recycled to the plasma membrane, where it encounters neutral pH conditions, APOL1 may form cation-selective channels. APOL1 is a member of a family of apolipoproteins which also includes six other proteins and it is a member of bcl2 genes which are involved in autophagic cell death. In fact an overabundance of APOL1 within a cell results in autophagy. APOL1 may play a role in the inflammatory response. Pro-inflammatory cytokines interferon-γ(IFN), tumor necrosis factor-α (TNF-α) and p53 can increase the expression of APOL1. APOL1 has a role in innate immunity by protecting against Trypanosoma brucei infection, which is a parasite transmitted by the