Our current study reveals that (1) TDAG51 expression is elevated in the distal anorectal region of colon tissues of DSS-induced experimental colitis model mice, (2) TDAG51 deficiency protects mice against DSS-induced lethality and body weight changes and disease severity, and (3) TDAG51 deficiency attenuates the production of inflammatory mediators in a DSS-induced experimental colitis mouse model. This evidence concerns the gene PHLDA1 and colitis.