Urologic pelvic pain syndrome (UCPPS), variably termed painful bladder syndrome/interstitial cystitis (PBS/IC) in females and chronic prostatitis/chronic pelvic pain syndrome in men (CP/CPPS), is a chronic, debilitating clinical syndrome presenting as severe pelvic pain with extreme urinary urgency and frequency in the absence of any known cause. The etiologic mechanisms underlying UCPPS are unknown, but recurrence, risks to siblings of affected individuals, concordance among monozygotic twins, and our own preliminary studies indicate a strong genetic contribution to the cause of UCPPS. The overall goal of this proposal is use novel approaches to understand the basis of UCPPS, to identify candidate genes containing mutations that result in UCPPS and determine how the different encoded proteins of these genes interact with one another in a common biological pathway. Ultimately, understanding how mutations in at least five different genes yield the symptoms of UCPPS should lead to improved diagnosis and possible therapies.