Kidney fibrosis marks a critical phase in chronic kidney disease with its molecular intricacies yet to be fully understood. This study's deep dive into single-cell sequencing data of renal tissue during fibrosis pinpoints the pivotal role of fibroblasts and myofibroblasts in the fibrotic transformation. Through identifying distinct cell populations and conducting transcriptomic analysis, Spp1 emerged as a key gene associated with renal fibrosis. The study's experimental findings further confirm Spp1's vital function in promoting fibroblast to myofibroblast differentiation via the TGF-β/Smad signaling pathway, underscoring its contribution to fibrosis progression. The suppression of Spp1 expression notably hindered this differentiation process, spotlighting Spp1 as a promising therapeutic target for halting renal fibrosis. This condensed summary encapsulates the essence and findings of the original research within the specified word limit.