When the pH in the culture medium was reduced from 7.8 to 6.5, the originally insensitive cell lines (including the cancer cell lines U251, SK-MEL-1, MCF7 and MDA-MB-231; and the noncancerous cell lines L929, HFL-1, HaCaT, and LX-2) became responsive to DM-αKG-induced pyroptosis (Fig. 7a and Supplementary information, Fig. S7c, d), exhibiting a pyroptotic morphology and GSDMC cleavage, possibly resulting from a significant increase in the L-2HG level (Fig. 7b), ROS level (Fig. 7c), DR6 oxidation (Fig. 7d), and caspase-8 activation (Fig. 7e) under acidic pH conditions in response to DM-αKG. Here, TNFRSF21 is linked to cancer.