<p>The acidic and inflammatory microenvironment serves as a central pathological feature of intervertebral disc degeneration (IVDD), acting as a critical driving factor in disease progression. However, the interplay between acidic and inflammatory microenvironments remains largely unexplored. In this study, we revealed the molecular mechanism by which crosstalk between glycolysis and pyroptosis exacerbates IVDD. We observed that lactic acid stimulation triggers pyroptosis in NPCs by stimulating the NLRP3 inflammasome, activating the caspase-1 pathway, and upregulating the expressions of IL-1β and IL-18. Acid sensitive ion channel 1a (ASIC1a) expression is positively correlated with extracellular acidosis severity and NPC pyroptosis levels. Furthermore, the knockdown of ASIC1a via siRNA effectively alleviated pyroptosis. After treatment of NPCs with IL-1β, glycolysis levels were increased, accompanied by up-regulation of c-Myc (a key regulator of the Warburg effect) and nuclear translocation, the knockdown of c-Myc effectively alleviated glycolysis. Mechanistically, lactate activates acid-sensing ion channel 1a (ASIC1a), which mediates Ca²⁺ influx to promote pyroptosis in nucleus pulposus cells (NPCs) and IL-1β release. Secreted IL-1β subsequently induces the nuclear translocation of, thereby upregulating glycolytic enzyme expression, enhancing glycolysis, and accelerating lactate accumulation. This cascade establishes a vicious cycle that progressively aggravates IVDD. Our findings demonstrate that glycolysis‒pyroptosis crosstalk promotes acid‒inflammatory microenvironments in degenerated discs, driving disease progression. Targeted inhibition of this crosstalk improves disc biological function and mitigates IVDD progression.</p>