Taken together, these results reveal a novel causal role of upregulated TP53RK, which correlated well with renal fibrosis and kidney function impairment, in promoting renal fibrosis through phosphorylation and nuclear translocation of Birc5 and thus enhancing cellular phenotypic alterations in both renal tubular epithelial cells and fibroblasts. Here, TP53RK is linked to renal fibrosis.