APOL5 (apolipoprotein L5) is a member of the apolipoprotein L gene family located on chromosome 22. While the precise physiological role remains incompletely characterized, APOL5 is proposed to affect lipid movement in the cytoplasm and facilitate lipid binding to organelles [UniProt]. Structurally, APOL5 shares conserved cation channel-regulating residues with other APOL family members; however, it exhibits distinct functional properties 1. Unlike APOL1, APOL3, and APOL6, APOL5 is non-cytolytic and does not induce cellular swelling 1. In planar lipid bilayers, APOL5 readily inserts into membranes at neutral pH in a voltage-dependent manner to form ion-conductive channels, suggesting specialized roles in innate immunity against specific pathogens under particular cellular conditions 1. Clinically, APOL5 expression changes are associated with IgA nephropathy progression; elevated APOL5 mRNA levels in glomeruli predicted disease progression with 88% accuracy and 100% specificity, up to 21 years before clinical manifestation 2. A heterozygous deletion encompassing the entire APOL5 gene was identified in a family with congenital heart disease, though RBFOX2 deletion within this region was implicated as the primary causative variant 3. These findings indicate APOL5 participates in immune responses and kidney disease pathogenesis, though mechanistic details warrant further investigation.