The goal of this proposal is to develop a RDCRC dedicated to myasthenia gravis (MGNet). Myasthenia gravis has a well-defined pathophysiology of autoantibody-mediated injury to the neuromuscular junction, but distinct sub-types exist with unique underlying pathophysiology and patient needs. Therapies exist but patient care is compromised by an absence of a cure, poor adverse effect profiles of treatments, highly variable response to existing treatments, and a poor quality of life as reported by patients. Further, therapeutic development in the field is compromised by a lack of adequate natural history data for all MG subtypes and a lack of treatment responsive biomarkers. Despite a few rigorously performed clinical trials, the failure of several phase 2 and 3 studies to support efficacy of drugs with validated biological targets indicates that MG trials require improvements in design and outcome measures. These challenges are made more difficulty by the existence of clinically and biologically distinct sub- types. These groups are 1) early-onset acetylcholine receptor (AChR) antibody (Ab) positive MG, which primarily affects women, 2) late-onset AChR Ab positive MG with a disease bias towards men 3) paraneoplastic thymoma-associated MG, 4) muscle specific kinase (MuSK) Ab positive, and 5) AChR/MuSK antibody negative MG. MGNet proposes the following Specific Aims: 1) Enhance clinical trial readiness through rigorous prospective monitoring of patients to define disease variability and refine clinical outcome measures. 2) Identify treatment-predictive and -responsive biomarkers to enhance early-phase clinical trial performance and identify suitable candidates for pivotal trials, improve monitoring in day-to-day clinical practice, and provide potential therapeutic targets. 3) Enhance the pool of young investigators focusing their careers on rare diseases and specifically MG. 4) Improve the awareness of scientists, physicians, and lay public regarding the unique needs of patients with MG. Successful achievement our objectives will establish a disease-specific infrastructure of biological samples and best practices which will provide a unique resource for academics and industry for access to biological samples for discovery purposes and development of clinical trials. During this process we will train clinician scientists and engage the patient and scientific communities in clinical research and therapeutic development.