We describe the structure of the QotM Challenges, provide an overview of the six challenges that have been conducted to date (topics were drug-induced liver injury, cannabidiol (CBD) toxicity, coronavirus infection, diabetes, psoriatic arthritis, and ATP1A3-related phenotypes), and highlight the benefits of this approach for simultaneously supporting the generation of scientific insights and the identification of technical gaps and weaknesses in the prototype Translator system. The gene discussed is ATP1A3; the disease is psoriatic arthritis.