In this study, we demonstrated that TRPV1—reported to be comparably expressed across the two OS cell lines in the Human Protein Atlas database of cancer cells (https://www.proteinatlas.org (accessed on 6 April 2025))—functions as a central node in the mechanotransduction machinery of OS cells, while showing no apparent role in mechanoregulation in healthy hFOB osteoblasts, for which no comparable expression data are available. Here, TRPV1 is linked to cancer.