Copper is essential for cellular function but potentially toxic in excess. While copper's influence on cytoskeletal dynamics remains unclear, loss of mechanical integrity is a hallmark of kidney disease. Here we investigated how copper availability modulates mechanical properties and cytoskeletal architecture of human proximal tubule epithelial cells (HK-2). Cells were treated for 24h with 50 µM CuCl₂ (copper supplementation) or 10 µM tetrathiomolybdate (TTM, copper chelation). Quantitative proteomics revealed coordinated changes in actin-regulatory proteins including Rab35, Septin2, MsrB2, and CK2 subunits, establishing redox-dependent pathways linking copper homeostasis to cytoskeletal dynamics. A total of 4,933 proteins were quantified with 89-90% data completeness, including detection of 13,919 PTMs per run (carbamidomethylation, oxidation, phosphorylation sites)