Post-translational protein S-palmitoylation in renal tubular injury: mechanisms and therapeutic implications

Renal tubular injury contributes substantially to the progression of acute kidney injury (AKI) and chronic kidney disease (CKD). S-palmitoylation is a reversible lipid modification that regulates protein localization, stability, trafficking, and signaling. In renal tubular epithelial cells (TECs), it supports epithelial polarity, ciliary function, ion transport, and receptor activity. During renal tubular injury, dysregulated S-palmitoylation can disrupt tubular homeostasis by altering epithelial cell responses. It may aggravate cell damage, amplify inflammation, and promote failed repair and fibrosis. Changes in renal vascular cells and podocytes may also influence tubular injury through renal perfusion and the glomerular filtrate. However, the effects of S-palmitoylation are not the same. Some changes promote injury, whereas others preserve tubular function or limit injury signaling. The outcome depends on the modified protein, the enzyme involved, and the renal cell type. This mini-review summarizes the physiological roles of S-palmitoylation in renal tubules, its direct and indirect contributions to tubular injury, and therapeutic strategies targeting palmitoyltransferases, depalmitoylases, and specific substrates. Because global modulation may disrupt protective pathways, future interventions should prioritize pathogenic enzyme-substrate pairs and cell-specific delivery.