The mechanisms behind the accumulation of colitogenic CD4<sup>+</sup> T cells are not fully understood, particularly regarding how regulators of intracellular versus extracellular metabolites can drive such responses.<h4>Main findings</h4>Here, we found that Pannexin-1 (PANX1) hemichannels, which promote ATP export to the extracellular environment, are crucial for the development of colitis. The gene discussed is CD4; the disease is colitis.