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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\u2019s cell biologic features, including questions and unaddressed aspects. This perspective may contribute to a deeper understanding of APOL1-associated cytotoxicity as well as AMKDs.<\/jats:p>","DOI":"10.3390\/cells14130960","type":"journal-article","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T10:44:41Z","timestamp":1750761881000},"page":"960","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A Cell Biologist\u2019s View on APOL1: What We Know and What We Still Need to Address"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1689-5462","authenticated-orcid":false,"given":"Verena","family":"H\u00f6ffken","sequence":"first","affiliation":[{"name":"Medical Clinic D, University Hospital M\u00fcnster, 48147 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela Anne","family":"Braun","sequence":"additional","affiliation":[{"name":"Medical Clinic D, University Hospital M\u00fcnster, 48147 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann","family":"Pavenst\u00e4dt","sequence":"additional","affiliation":[{"name":"Medical Clinic D, University Hospital M\u00fcnster, 48147 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Weide","sequence":"additional","affiliation":[{"name":"Medical Clinic D, University Hospital M\u00fcnster, 48147 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1016\/S0022-2275(20)31171-8","article-title":"Apolipoprotein L Gene Family: Tissue-Specific Expression, Splicing, Promoter Regions; Discovery of a New Gene","volume":"42","author":"Duchateau","year":"2001","journal-title":"J. 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