POP1 encodes a core structural component of ribonuclease P and MRP complexes, which process precursor tRNA by cleaving 5' leaders and cleave pre-rRNA sequences, respectively. Beyond its canonical RNA processing function, POP1 has emerged as a negative regulator of NLRP3 inflammasome signaling. POP1 directly binds the adaptor protein ASC via pyrin domain interactions, preventing inflammasome assembly and the subsequent activation of caspase-1 1. This inhibitory mechanism has therapeutic relevance: POP1 expression dampens monosodium urate crystal-induced inflammation in gout models, reducing neutrophil infiltration and IL-1β secretion 2, and overexpression of POP1 or engineered cell-permeable variants ameliorated disease severity in vivo 2. In cancer contexts, POP1 is upregulated in breast cancer tissues and promotes progression by stabilizing telomerase RNA, thereby maintaining telomere integrity during cell division 3. Biallelic POP1 mutations cause anauxetic dysplasia type 2, a rare autosomal recessive skeletal dysplasia characterized by severe short stature, metaphyseal dysplasia, and brachydactyly 4; recent evidence expands the phenotypic spectrum to include neurodevelopmental delay and multiple congenital anomalies 5. These dual roles—as a housekeeping RNA processing factor and an inducible immune checkpoint—position POP1 as both a developmental gene and a potential therapeutic target in inflammatory diseases.