NLRP inflammasomes are a group of cytosolic multiprotein oligomer pattern recognition receptors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) produced by infected cells. They regulate innate immunity by triggering a protective inflammatory response. However, aberrant activation of NLRP inflammasomes and gain-of-function mutations in NLRP sensor proteins are involved in the occurrence and enhancement of non-communicating autoimmune, auto-inflammatory, and neurodegenerative diseases. Recent advances have been made in understanding the physiological functions, molecular mechanisms of activation, and therapeutics targeting NLRP inflammasome activity in inflammatory diseases. This review provides an overview of the latest research progress on NLRP inflammasomes, including NLRP1, CARD8, NLRP3, NLRP6, NLRP7, NLRP2, NLRP9, NLRP10, and NLRP12, regarding their structural and assembling features, signaling transduction, and molecular activation mechanisms. It highlights the mechanisms associated with NLRP inflammasome dysregulation in various human auto-inflammatory, autoimmune, and neurodegenerative diseases. Overall, the review summarizes the latest discoveries in NLRP biology, their formation of inflammasomes, and their role in health and diseases, providing therapeutic strategies and perspectives for future studies on NLRP inflammasomes.NLRP inflammasomes are a group of cytosolic multiprotein oligomer pattern recognition receptors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) produced by infected cells. They regulate innate immunity by triggering a protective inflammatory response. However, aberrant activation of NLRP inflammasomes and gain-of-function mutations in NLRP sensor proteins are involved in the occurrence and enhancement of non-communicating autoimmune, auto-inflammatory, and neurodegenerative diseases. Recent advances have been made in understanding the physiological functions, molecular mechanisms of activation, and therapeutics targeting NLRP inflammasome activity in inflammatory diseases. This review provides an overview of the latest research progress on NLRP inflammasomes, including NLRP1, CARD8, NLRP3, NLRP6, NLRP7, NLRP2, NLRP9, NLRP10, and NLRP12, regarding their structural and assembling features, signaling transduction, and molecular activation mechanisms. It highlights the mechanisms associated with NLRP inflammasome dysregulation in various human auto-inflammatory, autoimmune, and neurodegenerative diseases. Overall, the review summarizes the latest discoveries in NLRP biology, their formation of inflammasomes, and their role in health and diseases, providing therapeutic strategies and perspectives for future studies on NLRP inflammasomes.