Abstract: Disclosed herein are methods of treating or preventing an autoimmune skin disorder and/or inflammatory skin disorder, skin tumor and obesity in a subject in need thereof by administering an inhibitor capable of inhibiting the activation of inflammasome NLRP1, NLRP1 mutants, an agent that prevents the secretion of stress responsive secreted factors, known pro-inflammatory cytokines, keratinocytes differentiation markers, inflammasome-dependent cytokines, and growth factors in the skin and an agent that reduces the effect of inflammasome-dependent cytokines. The invention encompasses the use of an activator of NLRP1, such as talabostat, specifically for treating skin tumors. Also enclosed herein are methods of determining the likelihood of a subject in developing an autoimmune skin disorder and/or inflammatory skin disorder comprising detecting NLRP1 mutation in a sample obtained from the subject. An inflammasome sensor NLRP1 mutant and compositions for treatment are also disclosed.