OTOP2 Proton Channel Couples Luminal pH Sensing to Intestinal Immune Homeostasis

mice exhibit increased susceptibility to dextran sulfate sodium (DSS)-induced colitis. Mechanistically, Otop2 deficiency reduces Paneth cell numbers and diminishes antimicrobial factor expression, likely due to impaired autophagy-lysosomal processes within these cells. Similarly, Otop2 deficiency impairs phagocytic function in bone marrow-derived macrophages (BMDMs). Together, these findings establish OTOP2 as a critical, pH-sensitive regulator of intestinal homeostasis and highlight its potential as a therapeutic target in IBD.