Notably, an orally bioavailable potent PTPN2/N1 active‐site inhibitor ABBV‐CLS‐484 (AC484) demonstrates significant therapeutic potential against ALK+ ALCL by disturbing mitochondrial renewal and blocking TFRC‐mediated PINK1‐PRKN‐dependent mitophagy to exert anti‐tumor activities, providing critical insights into the selection of targeted treatment strategies for ALK+ ALCL patients and a strong rationale for advancing AC484 into clinical trials. Here, PTPN2 is linked to anaplastic large cell lymphoma.