The current investigation elucidates PJA2 as a pivotal tumor suppressor gene in CRC, adding depth to its established significance in lung adenocarcinoma[33, 34] and its origin story as an E3 ubiquitin ligase linked to X‐linked mental retardation (MRX).[35] Beyond its downregulation in CRC, which positions it as a promising prognostic biomarker, PJA2's demonstrated capacity to restrain tumor proliferation and promote apoptosis underscores its potential as a universal tumor suppressor across a spectrum of malignancies. The gene discussed is PJA2; the disease is colorectal carcinoma.