SUMMARY This Research Training Program in Disease Oriented Neuroscience is designed to facilitate the transition between graduate training and a research-based career in neurology. R25 program trainees receive career mentoring from experienced clinician scientists in Neurology along with research mentoring from leading clinical neuroscience laboratory research faculty drawn from multiple departments and schools within the University of Pennsylvania. A focused educational program supplement laboratory research and includes training in translational research methods, applications, and the responsible conduct of research. The program is conducted in a large research-oriented institution with leading residency programs in adult and child neurology that trains some of the best candidates in the country and has an outstanding track record of fostering research oriented careers and trainee diversity. Over the past program period, the R25 pathway has been fully integrated into the residency training program and impacts all phases including residency application review, applicant visit and interviews procedures, advance mentorship and research opportunities for matriculated applicants, intensive support for the selection of mentors and the development of an R25 supplement request, and multiple levels of clinician scientist career development support. Between adult and child neurology, there are over 150 faculty members in our department, ranging from master clinicians, clinical educators, and clinical investigators to physician/scientists and basic scientists. Over 80% of graduating residents over the past 15 years have remained in academic medicine, and many have chosen careers as clinician scientists. The Hospital of the University of Pennsylvania and Children's Hospital of Philadelphia at the Perelman School of Medicine, where most of the clinical residency and fellowship training occurs, are located within a highly compact university campus in West Philadelphia spanning a radius of less than one half mile. Penn is also home to the first neuroscience institute in the country, the Mahoney Institute for Neurosciences, which consolidates almost 200 faculty members from 32 departments and six schools engaged in neuroscience research at Penn. The range of research opportunities for our R25 trainees can thus be extended to the wider neuroscience community inside and outside the Department of Neurology through co- mentorship of trainees with a diverse array of eminent scientists carrying out research relevant to the NINDS mission to reduce the burden of neurological disease.