PROJECT ABSTRACT This is an application from the Washington University to continue to be a clinical site for the second phase of the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN). The objectives of the LURN Study are to: (1) increase the understanding of lower urinary tract symptoms (LUTS) phenotypes and underlying mechanisms behind the patient subtypes and (2) develop a comprehensive, validated, and responsive measurement tools for defining treatment efficacy. After a successful initial 5-year funding cycle, LURN is prepared to build on the knowledge gained and take the next steps with the following Specific Aims: Aim 1: To refine and expand a clinically-relevant cluster model with a cohort of patients including wider range of symptom severity and a wider range of physiologic measures and followed for three years. Aim 2: To more deeply phenotype women with LUTS by measuring the functional components of the lower urinary tract (muscles of the bladder and urethra, and afferent and efferent nerves) in those with urinary urgency without incontinence, urinary urgency with incontinence, and normal controls. Aim 3: To identify a signature of proteins contained within plasma of specific subgroups of men and women with LUTS. Aim 4: To validate a comprehensive outcome tool for men and women with LUTS. Aim 5: To assess central sensitization in male and female patients with overactive bladder syndrome (OAB), compare their clinical phenotypes, cluster memberships, and serum protein signatures.