PROJECT SUMMARY Patients with gastroparesis often suffer with chronic symptoms that are not adequately treated due to both a lack of understanding of the underlying pathophysiology of gastroparesis and lack of effective treatments. Participation of Temple University as a clinical center in the NIDDK Gastroparesis Clinical Research Consortium (GpCRC) and Temple's proposed studies will help achieve the broad, long term objectives of improving the understanding and treatment of patients with gastroparesis. The PI and Temple University are well qualified to continue to be one of the clinical centers in the GpCRC. Temple University has extensive clinical expertise in gastroparesis and has been active in study development, enrolling patients into studies, manuscript publication, and obtaining funding for ancillary studies. The aims for Temple's renewal for the GpCRC are threefold. First, to continue enrollment and follow-up of patients in current GpCRC studies: GpR3, BESST, PBG, PSAG. We will maintain the Gastroparesis Registry 3 (GpR3) to enroll 400 patients with follow- up on patients for 1 to 4 years. GpR3 was recently enhanced to study the effects of SARS-CoV-2 in patients with gastroparesis. We continue to enroll in the clinical trial Buspirone for Early Satiety and Symptoms of Gastroparesis (BESST). Our Pathological Basis of Gastroparesis (PBG) is studying immune cell profiles in gastroparesis. We will start our study on pyloric pathophysiology: Pyloric Sphincter Abnormalities in Patients with Gastroparesis Symptoms (PSAGS). Second, to better understand the clinical manifestations and pathophysiology of patients with symptoms of gastroparesis, we will start a new registry, Gastroparesis Registry 4 for enrollment of 400 new patients. This application includes suggestions for five areas of study: 1) evaluating for autoimmune gastroparesis; 2) understanding meal eating characteristics and ARFID-like symptoms in patients with gastroparesis; 3) assess for hypocortisolism which can occur in gastroparesis patients and add to the symptom severity; 4) assessing for vagal and peripheral neuropathy as pathophysiologic comorbidities in gastroparesis; and 5) further enhancement of gastric emptying scintigraphy (GES) assessing antral synchronicity and antropyloroduodenal coordination. Third, to conduct a new multicenter study investigating the pathophysiology, diagnosis, and treatment of gastroparesis. Our application proposes a new study, Relating Gastric Pathophysiology using GES with DACS to Treatment Outcome, aimed at understanding the pathophysiologic basis of gastroparesis and its relationship to symptoms. The goal is to better target specific treatment based on pathophysiology and symptoms. Temple's participation and proposed studies will help achieve the goal of the NIDDK GpCRC to advance our understanding and treatment of gastroparesis.