PYDC2 (pyrin domain containing 2), also known as POP2, is a negative regulator of innate immune signaling. Structurally, it contains a pyrin domain that enables protein-protein interactions critical to its inhibitory functions 1. Primary functions include disrupting NLRP3 inflammasome assembly by binding to ASC and preventing recruitment of upstream sensors, thereby blocking caspase-1 activation and IL-1β maturation 1. PYDC2 additionally inhibits NF-κB signaling by reducing phosphorylation of RelA/p65 and impairing its nuclear accumulation, consequently suppressing production of TNF-α and IL-6 following toll-like receptor stimulation 2. PYDC2 also impairs macrophage priming through inhibition of non-canonical IκB kinase ɛ and IκBα signaling 1. Disease relevance involves autoinflammatory conditions; however, genetic association studies show limited direct correlation—PYDC2 variants were not associated with Behçet's disease in a Turkish cohort 3. Recent exploratory whole exome sequencing identified PYDC2 among candidate genes potentially differentiating autism spectrum disorder from other developmental disorders, though replication in larger cohorts is necessary 4. Clinically, PYDC2's anti-inflammatory function suggests therapeutic potential for inflammasome-driven inflammatory diseases, though direct clinical applications remain undetermined.