MEFV encodes pyrin, a critical regulator of innate immunity and inflammatory responses. Pyrin functions through dual mechanisms: it serves as a platform organizing autophagic machinery by assembling ULK1, Beclin 1, ATG16L1, and ATG8 family members 123, and acts as an autophagy receptor degrading inflammasome components including CASP1, NLRP1, and NLRP3 to prevent excessive IL-1β and IL-18 production 123. Conversely, pyrin also positively regulates inflammation by triggering PYCARD/ASC specks formation, caspase-1 activation, and inflammatory cytokine production 456. MEFV mutations cause familial Mediterranean fever (FMF), an autosomal recessive autoinflammatory disease characterized by recurrent fever and serositis, with amyloidosis as the major complication 7. Beyond FMF, MEFV mutations associate with rheumatoid arthritis severity 8, neuro-Behçet's disease 9, palindromic rheumatism 10, and gouty arthritis 11, suggesting pleiotropic roles in various rheumatic conditions. Colchicine remains the primary therapeutic agent for FMF, effectively reducing amyloidosis development and attack frequency 7.