NLRP1 (NLR family pyrin domain containing 1) is an innate immune sensor and inflammasome nucleator primarily expressed in skin and airway epithelium 1. It functions as a molecular sentinel that detects cellular stress and pathogenic threats, triggering inflammasome assembly—a critical platform for activating inflammatory caspases and processing proinflammatory cytokines 2. NLRP1 senses ribotoxic stress responses induced by ultraviolet B radiation and microbial toxins through phosphorylation by the MAP3K ZAKα kinase and its downstream effector p38 13. Phosphorylation at serine 107 in the linker region is critical for activation, followed by ubiquitination and N-terminal degradation, generating the functional inflammasome nucleator NLRP1UPA-CARD 3. NLRP1 also responds to alphavirus infection, including Semliki Forest and Chikungunya viruses, through p38-mediated activation 3. Upon activation, NLRP1 orchestrates caspase-1-mediated maturation and secretion of IL-1β and IL-18, driving pyroptotic cell death as an innate immune defense mechanism 45. Dysregulation of NLRP1 inflammasome activity contributes to multiple autoinflammatory and autoimmune diseases, including those affecting skin and respiratory epithelium, highlighting its clinical importance in immune homeostasis.