DUSP13B (dual specificity phosphatase 13B) is a testis-specific dual specificity phosphatase that functions as a negative regulator of stress-activated MAPK signaling pathways. The protein exhibits intrinsic phosphatase activity toward both phospho-seryl/threonyl and phospho-tyrosyl residues and specifically dephosphorylates MAPK8/JNK and MAPK14/p38, but not MAPK1/ERK2 1. DUSP13B is most highly expressed in testis, particularly in spermatocytes and round spermatids, where it protects cells from external stress during spermatogenesis by inhibiting stress-activated MAPKs 1. Mechanistically, DUSP13B suppresses AP-1-dependent gene expression and can be upregulated by myogenin to provide cardioprotection against oxidative stress-induced apoptosis through p38 MAPK inactivation 12. The protein also interacts with STAT3 and modulates its phosphorylation, playing a role in cancer drug resistance through the SHH/DUSP13B/p-STAT3 signaling axis 3. Clinically, DUSP13B shows therapeutic potential as a target for cardiovascular diseases with metabolic disorders and has predictive value for osimertinib resistance in NSCLC 43. The enzyme represents the first identified testis-specific phosphatase that inhibits stress-activated MAPKs.