DTD2 (D-aminoacyl-tRNA deacylase 2) is a tRNA deacylase that removes mischarges from aminoacyl-tRNAs to maintain translational fidelity. The enzyme deacylates D-aminoacyl-tRNAs and mischarged glycyl-tRNA(Ala), protecting cells against glycine mischarging by AlaRS 1. DTD2 exhibits relaxed substrate specificity due to a trans conformation of its Gly-Pro motif, enabling deacylation of L-alanine mischarged on tRNA(Thr) by alanine-tRNA ligase 1. By recycling D-aminoacyl-tRNA to free amino acids and tRNA molecules, DTD2 counteracts D-aminoacyl-tRNA toxicity and enforces protein L-homochirality. Clinically, DTD2 has emerged as a disease biomarker. IgG autoantibodies against DTD2 peptides are elevated in anti-SSA antibody-negative Sjögren's disease (SSA- SjD), with significantly higher binding in SSA- SjD cases compared to controls (p=0.003-0.004), and predict abnormal labial salivary gland pathology (p=0.012) 23. Anti-DTD2 autoantibodies combined with clinical variables achieve 74% AUC discrimination for SSA- SjD diagnosis and 72% AUC for predicting biopsy abnormalities 3. DTD2 is also recognized as a novel autoantigen in primary Sjögren's syndrome, offering diagnostic value for seronegative cases 4. In papillary thyroid carcinoma, DTD2 was identified as a significant early-stage disease marker through machine learning analysis 5. These findings position DTD2 as both a functional regulator of translational accuracy and an emerging diagnostic biomarker for autoimmune and neoplastic diseases.