IL1B and functional neutrophil defect: (31) demonstrated that the E2 enzyme UBE2L3 normally tags pro-IL-1β for K48-linked degradation; genetic or pharmacological loss of UBE2L3 stabilised the cytokine precursor, producing excess IL-1β and neutrophilic disease after NLRP3 activation Complementary work shows that mixed ubiquitination of NLRP3 by the gp78/Insig-1 E3 complex restrains sensor oligomerisation, so impaired ubiquitin charging likewise prolongs inflammasome stability (32).