This project investigates the role of Nuclear Factor I C (NFIC) in nuclear proteostasis, cellular aging, and domain-specific protein interaction networks using quantitative proteomics based on 4D Fast Data-Independent Acquisition (4D Fast DIA) mass spectrometry. For global nuclear proteome profiling, human lung fibroblast IMR-90 cells at different cellular states were analyzed. Samples NFIC01–NFIC06 represent nuclear proteomes quantified by 4D Fast DIA proteomics. Among them, NFIC01–NFIC03 correspond to the early-passage (EP, young) group, while NFIC04–NFIC06 correspond to the late-passage (LP, senescent) group. These datasets were generated to characterize age-associated alterations in the nuclear proteome and to explore NFIC-related molecular changes during cellular senescence. To further dissect the functional domains of NFIC and define its protein interaction landscape, immunoprecipitation (IP)–associated proteomic analysis was performed in HEK293T cells. Samples NFIC07–NFIC09 represent IP-derived proteomic datasets from cells expressing Flag-tagged eGFP (control), eGFP-NFIC (full-length), and eGFP-NFICΔIDR2 (IDR2 deletion mutant), respectively. These experiments were designed to compare the interactomes of full-length NFIC and its intrinsically disordered region 2 (IDR2) deletion variant, thereby defining the contribution of IDR2 to NFIC-mediated protein interactions.