In a dextran sodium sulfate (DSS)‐induced colitis model, wild‐type mice treated with ectosomal‐Calhm6 on alternate days exhibited significant resistance to colitis, as evidenced by improved disease activity index (DAI) scores, reduced colonic epithelial shedding, diminished inflammatory cell infiltration, and less weight loss and rectal bleeding (Figure S2B–D, Supporting Information). Here, CALHM6 is linked to colitis.