ABSTRACT Support is requested for a Keystone Symposia conference entitled Type 2 Diabetes: Understanding its Early Drivers and the Road to Therapeutics, organized by Drs. Christopher Rhodes, Lora Heisler, and Martin Myers. The conference will be held in Palm Springs, CA from May 1 - 4, 2023. Early detection and consequential intervention are key to good treatment outcomes and avoidance of complications for most diseases. Arguably, this may not be the case for Type-2 diabetes (T2D) where measures of elevated glucose and HbA1C, historically related to a predicted onset of retinopathy, occur too late in the pathogenesis of the disease. This makes the need for improved markers of T2D necessary to better diagnose and treat this prevalent disease at early stages. With the advent of precision medicine, now is the time to re-examine the pathogenesis of type 2 (pre)diabetes at the molecular level. However, questions the field remain, such as: 1. Which subsets of T2D define the rate of progression to certain diabetes complications; 2. Can early molecular drivers of the disease be better identified; 3. What factors contribute to dysfunctional inter-organ communication and altered metabolic homeostasis; 4. Does pancreatic ß-cell failure really define the disease; and 5. If detected early enough, can we envision ways to reverse, or even prevent T2D? The silver lining is that with several commonly used T2D therapies coming off patent soon, this may just be conceivable. Nonetheless, there also remains a need for more effective therapeutic approaches, not just for T2D, but also for its comorbidities. Therefore, this Keystone Symposia conference will examine the current knowledge of T2D pathogenesis and the therapeutic landscape with a vision towards earlier diagnosis, as well as, towards more effective and tailored T2D treatment regime(s) that could also prevent (or significantly delay) the pathway to complications and comorbidities.