DUSP22 (dual specificity phosphatase 22) is a dual-specificity phosphatase that dephosphorylates both phosphotyrosine and phosphoserine/threonine residues 12. Functionally, DUSP22 acts as a negative regulator of T-cell receptor (TCR) signaling by inactivating the tyrosine kinase Lck through direct dephosphorylation 1. DUSP22 additionally restrains immune activation by dephosphorylating the E3 ubiquitin ligase UBR2 at specific serine residues, triggering UBR2 proteasomal degradation and inhibiting UBR2-mediated Lys63-linked ubiquitination of Lck 2. While DUSP22 activates JNK signaling 3, it suppresses broader T-cell-mediated immune responses, with DUSP22 downregulation observed in systemic lupus erythematosus (SLE) patient T cells 4. Beyond immunological functions, hepatic DUSP22 mitigates nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma progression by dephosphorylating focal adhesion kinase (FAK) and suppressing ERK1/2 and NF-κB signaling 5. Clinically, DUSP22 alterations are associated with cutaneous CD30+ lymphoproliferative disorders; DUSP22-IRF4 translocations characterize lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large cell lymphoma, with DUSP22 functioning as a tumor suppressor through apoptosis induction and growth inhibition 67.