Proteins differential expression in type 2 diabetes mellitus (T2DM) can be due to etiological factors or pathological changes, such proteins can be utilized as biomarkers. Identification of a marker protein out of thousands became a feasible task during the proteomics era by using liquid chromatography-tandem mass spectrometry (LC-MS/MS). In this study, blood samples were obtained from 80 Bahraini subjects with and without T2DM, a subset was used for proteomic analysis by LC-MS/MS, while all samples were used for ELISA analysis of 3 proteins, TATA-box binding protein-associated factor RNA polymerase-1-C (TAF1C), ceruloplasmin (CERP) and fibronectin (FN). The former 2 proteins were selected from the T2DM-protein-panel identified by LC-MS/MS, and the latter was analyzed for validation of the setting. The main findings of the proteomic analysis are i. Identifications of 62 differentially expressed proteins in T2DM, ii. Upregulation of 71% of the identified proteins. While the ELISA analysis showed that; both TAF1C and FN were significantly increased in T2DM (P0.015 and P0.001, respectively), while CERP was not (P0.088). Logistic regression analysis: i. confirmed the above associations after correction for covariates, ii. Revealed an interaction between age and gender that affect the association of the proteins with T2DM. In conclusion, knowing that TAF1C is a prerequisite in ribosomal biogenesis, our ELISA results are suggestive of increased protein synthesis in T2DM, explaining the observed upregulation of the proteins identified by LC-MSMS. The association between T2DM and TAF1C is a novel finding that might open a new avenue in DM research. © 2019