Our work demonstrates for the first time, a clinical and biological role of TMEM30A in human cancer. The study, which was led by Daisuke Ennishi and Shannon Healy, uncovers clinically relevant mutations in DLBCL patients, and through the use of knockout mouse models and drug assays provide new biological insights into membrane physiology in B-cell lymphoma development and mutation-associated cellular vulnerabilities that can be therapeutically exploited.