Abstract
APOL1 is the most recent member of the APOL gene family and is expressed exclusively in humans and a few higher primates. More than twenty years ago, it was discovered that APOL1 protects humans from infections by trypanosome subspecies that cause African sleeping sickness. Interestingly, by a co-evolutionary process between parasite and host, two APOL1 variants emerged, which, in addition to their trypanotoxic effects, are simultaneously associated with a significantly increased risk for various different kidney diseases, which are now summarized as APOL1-mediated kidney diseases (AMKDs). The aim of this review is to highlight and formulate key aspects of APOL1's cell biologic features, including questions and unaddressed aspects. This perspective may contribute to a deeper understanding of APOL1-associated cytotoxicity as well as AMKDs.